bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT-046 Insulin-Like Growth Factor and Fibroblast Growth Factor 21 in Men with Klinefelter Syndrome
Authors: Chang Simon , Hjortebjerg Rikke , Bojesen Anders , Bjerre Mette , Gravholt Claus Hojbjerg
Published: May 2020

Background: Men with 47, XXY Klinefelter syndrome (KS) commonly present with obesity, metabolic disorders, and insulin insensitivity. The insulin-like growth factor (IGF) system has pleiotropic effects including regulation of glucose metabolism. Fibroblast growth factor 21 (FGF21) is associated with weight loss and favourable metabolic changes, but patients with obesity or type 2 diabetes might be resistant to this effect despite presenting with increased levels. Aim: To describe levels of components in the IGF system and FGF21 among men with KS, either treated or not treated with testosterone supplementation therapy (TT), in comparison with control males. Methods: A total of 66 men with KS were included, 33 without current TT and 33 with current TT. A control group of 70 healthy age-matched males were included. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP3), pregnancy-associated plasma protein A (PAPP-A), FGF21, and fibroblast activation protein (FAP) were compared between the three groups applying the Kruskal-Wallis test. Results: Levels of (IGF-1 µg/L) were not different between the groups (median (25-75 %), untreated KS 162 (140-201.5), treated KS 165 (128.5-215), controls 176.5 (150.8-214.5), p=0.5). Similarly, FGF21 levels (ng/L) were comparable between the groups (median (25-75 %), untreated KS 84.7 (53.3-217.6), treated KS 97.2 (56.4-224.8), controls 100.3 (66.0-191.0), p=0.9). Levels of IGFBP3, PAPP-A and FAP were also found to be comparable between the groups (p≥0.2). Conclusion: This was the first study investigating FGF21 in men with KS. Our results indicate that regulation of the IGF-1 system and levels of FGF21 are not altered in men with KS compared with age-matched controls, and that TT in men with KS does not affect these systems.
SUN-138 Functional Characterization of Tumor-Associated Germline TMEM127 Variants Reveals Novel Insights into Membrane Topology and Protein Trafficking
Authors: Flores Shahida , Zhang Xingyu , Cheng Ming , Dahia Patricia L
Published: May 2020

TMEM127, a tumor suppressor gene in hereditary pheochromocytomas and paragangliomas, encodes for a poorly characterized, ubiquitous, transmembrane (TM) protein with no substantial identity to any other protein and no identifiable functional domains other than putative TM domains. The function and regulation of TMEM127 remain poorly defined which limits prediction of pathogenicity of germline TMEM127 variants. Characterizing structure-function features of TMEM127 is relevant for understanding how dysfunction of this tumor suppressor can lead to inherited tumors. Moreover, a better understanding of TMEM127 functional domains and critical residues will increase our ability to identify pathogenic variants which will improve interpretation of genetic screening results and help guide clinical decisions for patients and their families. In this study, we investigated subcellular localization and steady-state levels of patient-derived, tumor-associated, germline TMEM127 variants (n=21; 16 missense and 5 truncating/frameshift/indel variants). We used confocal immunofluorescence and immunoblot analysis of GFP-TMEM127 constructs expressed in HEK293T cells. Wild-type (WT) TMEM127 localized predominantly to endo-lysosomal vesicles (punctate) with some plasma membrane localization. The localization of variant TMEM127 proteins displayed three distinct patterns: punctate (similar to WT), diffuse (cytoplasmic), and plasma membrane only. All diffuse proteins, and a few punctate proteins, decreased at a faster rate than the WT suggesting instability. Variants resulting in diffuse proteins occurred within TM domains and indicated that membrane binding ability was lost. This observation, supported by in silico analysis and selective permeability assays, led us to conclude that TMEM127 is a four-TM protein, not a three-TM protein, as previously predicted, with a novel TM domain in the N-terminus. One variant with predominantly plasma membrane localization indicated that membrane binding ability was maintained but internalization capability was lost. We identified an atypical, extended acidic dileucine motif in the C-terminal which is responsible for TMEM127 internalization and showed that it is mediated by clathrin. Our findings provide novel insights into structure-function features of TMEM127 which will allow for better understanding of its physiological role and improved prediction of pathogenic variants.
SUN-030 Tetraorchidism: A Rare Type of Polyorchidism
Authors: nagaraja soumya , Accacha Siham D , Angulo Moris Alejandro , George Sarita
Published: May 2020

Polyorchidism is defined as the presence of two or more testis. We report an interesting case of Tetraorchidism an extremely rare type of Polyorchidism in a 14-year-old boy with short stature due to Growth hormone deficiency. An extensive review of literature yielded only 200 case reports of Polyorchidism [1]. Most of these are case reports on triorchidism (3 testicles). There has been only 9 case reports of patients with (tetraorchidism) 4 testicles [2]. Most of them has been reported as incidental findings in adults.

This case is being reported due to its rarity. Here we elaborate on clinical presentation of Polyorchidism in children and their management plan. More specifically from Pediatric Endocrinology perspective, we discuss the influence of the Polyorchidism on the Tanner staging (by testicular volume), growth and pubertal development in boys.

Reference:

1. Amanda Myers, Bradley Morganstern and Ronnie Fine Urology, 2017-06-01, Volume 104, Pages 196-197,

2. Ibrahim H., Roberts M.J., and Hussey D.: Quadruple orchidopexy for torsion testis in an adolescent with polyorchidism: a case report. Urology 2016; 87: pp. 196-199.
SAT-241 Pituitary Stalk Interruption Syndrome Presenting as Neonatal Hypotonia
Authors: Bilbao Nordie Anne
Published: May 2020

Pituitary stalk interruption syndrome (PSIS) is a rare condition that include congenital anatomic abnormalities of the pituitary gland and hypopituitarism. There is a wide variety of clinical presentation, with the age at presentation encompassing from neonatal period to adulthood and including one or more pituitary hormone deficiencies. In recent literature there is increasing recognition of PSIS presenting in the neonatal period, mostly involving hypoglycemia. Our patient is a full-term male infant who presented in the newborn period with hypotonia and hypothermia. He also had hypoglycemia, which was initially thought to be associated to hyperinsulinism in the context of gestational diabetes. Micropenis was noted on physical exam. As part of the study for hypotonia, serial thyroid function tests were obtained revealing central hypothyroidism. A low dose ACTH stimulation test was performed which revealed adrenal insufficiency. The patient was started on cortisol and thyroid hormone replacement. Brain MRI showed an ectopic neurohypophysis located along the floor of the hypothalamus, a small anterior pituitary gland, and a partially absent infundibulum, findings consistent with pituitary stalk interruption syndrome. The patient received testosterone injections for micropenis and is being followed for development of other pituitary hormone deficiencies. PSIS is a rare congenital condition that is increasingly recognized in neonates manifesting with signs of hypopituitarism.
MON-330 Cancer Incidence in 1,296 Patients with Acromegaly Is Not Increased: A Nationwide Population-Based Study
Authors: Esposito Daniela , Ragnarsson Oskar , Johannsson Gudmundur , Olsson Daniel S
Published: May 2020

Background: Single- and multi-center studies have shown an increased incidence of malignancies in patients with acromegaly. These findings may be affected by selection bias. Our aim was therefore to investigate the incidence of malignancies in a nationwide unselected cohort of patients with acromegaly.

Methods: Adult patients diagnosed with acromegaly due to a pituitary tumor between 1987 and 2017 were identified in the Swedish National Patient Registry. All malignancies following the diagnosis of acromegaly were identified in the Swedish Cancer Registry that has a coverage of over 96%. Standardized incidence ratios (SIRs) for malignancies, with 95% confidence intervals (CI), were calculated by using the Swedish general population as a reference. Incidence of malignancies was also analyzed in sub-groups of patients treated with radiotherapy and in those having diabetes mellitus and hypopituitarism.

Results: A total of 1,296 patients with acromegaly were included (621 men, 675 women). The mean age (±SD) at diagnosis was 51.6±14.7 years. The mean follow-up was 12.7±8.3 years, with a total of 16,395 person years at risk. Pituitary surgery was performed in 842 (65%) patients and radiation therapy in 152 (12%) patients. The diagnosis of hypopituitarism and diabetes mellitus was recorded in 29% and 16% of patients, respectively. Overall, 186 malignancies were identified in patients with acromegaly as compared to 179 expected malignancies in the general population (SIR 1.04; 95% CI 0.90-1.20). Incidence of malignancies was similar in men and women [SIR 1.08 (95% CI 0.88-1.32) vs 1.00 (95% CI 0.80-1.23)]. Incidence of colorectal cancer (SIR 1.12; 95% CI 0.75-1.62) or malignancies of the respiratory system (SIR 1.22; 95% CI 0.76-1.84) was not increased. Incidence of kidney and ureter cancer (n=17) was, however, increased (SIR 3.81; 95% CI 2.22-6.11). In the entire study cohort, only three cases of thyroid cancer were recorded. SIR for malignancies in patients treated with radiotherapy (1.12; 95% CI 0.56-2.01) and in patients with hypopituitarism (SIR

0.91; 95% CI 0.68-1.18) or diabetes (SIR 1.08; 95% CI 0.78-1.45) did not differ from the general population.

Conclusions: This large nationwide population-based study showed that the overall incidence of malignancies in patients with acromegaly was not different from the general population. In particular, incidence of colorectal and thyroid cancer was not increased. Incidence of malignancies of the urinary tract was, however, increased.
MON-136 Reducing Unnecessary Inpatient Adrenocorticotropin Stimulation Tests
Authors: Ali Ridha , Lochnan Heather Anne , Shaw Julie , Tran Christopher S
Published: May 2020

Background:

Outpatient adrenocorticotropin (ACTH) stimulation tests can be challenging to interpret due to heterogeneously reported cut-offs. Inpatient stimulation tests present additional challenges due to the presence of acute illness and unreliable coordination of dynamic function testing on a busy inpatient service. This study aims to characterize the use of ACTH stimulation tests in hospitalized patients to determine necessity of testing.

Methods:

We conducted an inpatient audit of ACTH simulation tests done to rule out adrenal insufficiency between April 2018 to March 2019 at our institution. Normal post-ACTH response was defined as peak cortisol ≥500 nmol/L. Testing was considered inappropriate in patients with normal post-ACTH response who had a serum cortisol ≥250 nmol/L drawn during the same admission prior to stimulation testing. Cut-offs were based on previous analysis of 195 outpatient stimulation tests.

Results:

During the one-year study period there were 40 inpatients who had an ACTH stimulation test. Nineteen (48%) were considered unnecessary because patients either had a pre-ACTH serum cortisol ≥250 nmol/L and/or a 0-minute cortisol value just prior to the ACTH stimulation test ≥250 nmol/L. Except for a single instance where the patient was inappropriately on prednisone when basal cortisol was tested, all patients with any pre-ACTH cortisol ≥250 nmol/L had a normal post-ACTH response

Conclusion:

Institutions may avoid unnecessary inpatient ACTH stimulation tests by implementing protocols which ensure that basal cortisol levels are drawn and below locally determined cut-offs before proceeding to dynamic testing. To characterize further, a three-year analysis of inpatient ACTH stimulation tests is underway.
SAT-665 A Case of Hyperglycemia in Post Pancreas Transplant Patient-Is It Insulin Deficiency or Insulin Resistance
Authors: Polavarapu Preethi , Boerner Brian
Published: May 2020

Introduction

Pancreatic transplant (PTx) is a less commonly utilized option for patients with Type 1 Diabetes (DM1), usually with co-morbid end stage renal disease. Hyperglycemia in the post-PTx population can be multifactorial. We report a case of hyperglycemia with ketosis in a post-PTx patient due to insulin resistance and relative insulin deficiency.

Case Presentation

55-year-old male patient with DM1 who underwent simultaneous kidney-PTx. His immunosuppressant (IS) medications were tacrolimus, mycophenolate and prednisone. Tacrolimus levels were therapeutic and his transplant course was benign. He did not require insulin or other glucose-lowering medications post-PTx for 29 years. However, during evaluation for subacute illness with his PCP, he was found to have HbA1c of 12.6%, plasma glucose (PG) 776 mg/dl, and positive urine ketones. He was started on insulin degludec 24 units daily, which was quickly tapered to 8 units daily due to hypoglycemia. OGTT showed fasting PG of 93 mg/dl, 2-hour PG of 115 mg/dl, and stimulated C-peptide of 7.5 ng/ml. HbA1c improved to 7.4% after being on insulin for 1 month. Insulin degludec was tapered and discontinued within 2 months due to hypoglycemia despite low doses and robust PTx function. Home blood glucoses (BG) were controlled and HbA1c stable at 6% off insulin therapy. Eighteen months later, he was hospitalized for hyperglycemia with ketosis, without acidosis, during an upper respiratory infection. He was restarted on insulin (glargine, aspart). Once the acute stress resolved, his insulin dose needs reduced significantly, tapering down to insulin glargine 5 units daily. Along with daily home BG monitoring, HbA1c and C-peptide are performed every 3 months, with recent HbA1c 5.2% and C-peptide 3.0 ng/ml (simultaneous PG of 103 mg/dl).

Discussion

Causes of post-PTx hyperglycemia include graft failure due to acute or chronic rejection, insulin resistance, beta cell dysfunction due to IS medications, pancreatitis, or, rarely, recurrence of autoimmunity. Factors predicting hyperglycemia are pre-PTx insulin dose, BMI and acute rejection. New onset type 2 diabetes can occur due to insulin resistance from IS medications and genetic predisposition. Measurement of C-peptide after OGTT can help determine the cause. Insulin is the standard treatment even with detectable C-peptide, though oral glucose-lowering medications have been used in the setting of insulin resistance. In this patient, severe hyperglycemia occurred during stress. He had very low insulin dose requirements when the stress and hyperglycemia resolved and reasonable C-peptide values. This scenario was most consistent with hyperglycemia due to insulin resistance and subsequent relative insulin deficiency during stress, with continued PTx function. This illustrates the importance of detailed assessment and personalized treatment in patients with post-PTx hyperglycemia.
SUN-159 17-beta Hydroxysteroid Dehydrogenase 3 Deficiency in 1 Month Old Infant
Authors: Mathew Deepa , Speiser Phyllis Witzel , Panayiotopoulos Aristotle , Pisani Laura
Published: May 2020

Background: 17-beta hydroxysteroid dehydrogenase 3 deficiency is a rare autosomal recessive disorder caused by mutations in HSD17B3 encoding the enzyme which converts androstenedione to testosterone. It is characterized in 46, XY males by incomplete virilization, including micropenis and hypospadias.

Clinical Case: We report a 1 month old infant who presented with ambiguous genitalia. Prenatal non-invasive screening showed a Y chromosome, however, fetal ultrasound revealed female genitalia. The infant was born with micropenis (~1.4 cm in length) and proximal hypospadius, with enlarged labioscrotal folds and palpable gonads bilaterally. The urethral meatus had been relocated surgically to the glans. There was an apparent vaginal orifice with a normally positioned anus. Initial testing revealed a normal serum 17-OHP (90 ng/dl, n<200 ng/dl) and normal electrolytes. Abdominal US showed normal kidneys. Pelvic US demonstrated no Mullerian structures; gonads thought to be testes were identified in the labioscrotal folds. At 3 months of age, the infant underwent a 3 day HCG stimulation testing with a borderline testosterone response to 132 ng/dl, androstenedione 78 ng/dl and DHT 25 ng/dl. T/A ratio was unremarkable at 1.7 (n>0.8). Thus, hormonal testing was unsupportive of a testicular steroidogenic enzyme deficiency or androgen insensitivity syndrome. Karyotype was confirmed as 46, XY with microarray evidence of multiple regions of homozygosity. Genotyping with a 46, XY DSD panel (GeneDx) revealed a homozygous pathogenic variant c.608 C>T (p.A203V) in exon 9 of the HSD17B3 gene, consistent with a diagnosis of autosomal recessive 17-beta hydroxysteroid dehydrogenase 3 deficiency. Parents are of Arabic descent and are consanguineous. An older brother was also born with ambiguous genital and was later found to be homozygous for the same mutation. This mutation has been identified in the homozygous state in several unrelated affected patients. Previously published functional studies demonstrated loss of enzymatic activity with this missense mutation (1). Male gender was assigned at birth, and parents wish to continue male sex of rearing.

Conclusion: Molecular genetic analysis utilizing a commercially available candidate gene panel for 46, XY disorders of sex development diagnosed 17 beta-HSD3 deficiency in this case where hormonal testing was not informative. Early and correct diagnosis is key in planning medical treatment to facilitate pubertal development.

References: (1) Geissler et al., 1994 Nature Genetics 7(1): 34-9.
SAT-357 First Case in Saudi Arabia Revealing Fahr Syndrome Secondary to Hypoparathyroidism: A Case Report
Authors: Khan Soha , Alhamdan Ali Saleh , AlGhamdi Ahmed , AlShehri Abdulleh , Douba Najah , AlAblani Hamad , Husain Ahmed Z
Published: May 2020

Introduction: Fahr Syndrome is a rare inherited or sporadic neurological disorder. It is characterized as in abnormal calcium deposition or in other words, calcification in the brain which almost always occurs bilaterally. Patients with Fahr syndrome usually presents with neurological symptoms such as seizures, tetany, speech impairment, dementia, deterioration of intelligence, involuntary movements. The etiology of Fahr syndrome is mostly associated with endocrine disorders especially hypoparathyroidism either primary or secondary or pseudo hyperparathyroidism; including adult onset neurodegenerative conditions, infectious disease like intrauterine and perinatal infections or inherited congenital causes are also considered.

Clinical Case The authors report a 33-year-old Ethiopian female not known to any medical illness presented with abnormal involuntary left-hand movement, headache and dizziness. Further examination shows positive Chvostek’s and Trousseau’s signs. In addition, laboratory findings reveal decreased levels of serum calcium (1.227 mmol/L, normal range of 2.2-2.65 mmol/L), serum albumin (33.53 mg/dL, normal range of 35-52 g/L) and parathyroid hormone (0.3pmol/L, normal range of 1.1-8.43 pmol/L), decreased vitamin D serum level (14.52 ng/ml, normal range of 30-75 ng/ml). Interestingly, brain imaging shows bilateral symmetrical subcortical white matter, basal ganglia, cerebellar dentate nuclei calcifications. Thus, Fahr syndrome diagnosis was made. She was promptly treated with calcium and vitamin D replacement. Calcium gluconate was given intravenously with oral calcium carbonate and oral cholecalciferol. The patient recovered with this treatment leading to positive results without any recurring symptoms.

INTERNAL

Conclusion In conclusion, Fahr syndrome is a rare sequel of hypoparathyroidism, mostly presented with neurological symptoms due to hypocalcemia which after correction subdues the occurring manifestation such as in this case presented. Early diagnosis of Fahr syndrome due to hypoparathyroidism is crucial for prompt treatment and reversal of symptoms also to prevent complications.

INTERNAL
SUN-714 Phenotype of Patients Carrying the c.709(-7-2)del PRKAR1A Mutation in a Large Cohort of 41 Patients
Authors: Abderrahmane Fatimetou , Raverot Gerald , Lefebvre Herve , Catherine CARDOT , Vantyghem Marie-Christine , Bertherat Jérôme , Espiard Stéphanie
Published: May 2020

Objective: The Carney Complex (CNC) is a multiple endocrine and non endocrine neoplasia, mostly due to PRKAR1A mutations. The PRKAR1A mutation c.709(-7-2)del located in the intron 7 is one of the three known hot spot. The objective of this study is to described the CNC manifestations presented by patients harboring the c.709(-7-2)del. Methods: This study is a multicenter retrospective longitudinal study. Patients data have been collected from medical files. Multicenter retrospective study. Age at the diagnosis or at the screening of the different CNC manifestations is described by mean +/- standard deviation or median (interquartile) according to the distribution. Results: 41 patients [14 index cases and 37 relatives, 29 females, 43.6 ±14.3 years old (yo)] from 15 families have been included. 58% of the cohort including the 14 index cases presented with a primary pigmented adrenal disease (PPNAD) at 24-yo (18-40). For the remaining 17 patients, only 3 patients had normal glucocorticoid biological evaluation while others presented with subclinical hypercortisolism diagnosed at 35-yo (22-50). 7% of the cohort had an abnormal IGF1 and/or GH after oral glucose tolerance test while other patients had normal evaluation with a last test performed at 41 ±15yo. 22% of patients presented with lentigines diagnosed at 43yo (24-51) while others had no dermatological lesions at the last examination performed at 37 ±14yo. 13% of patients had thyroid nodules or papillary carcinoma diagnosed at 46 ±15yo (normal ultrasound for others at 37 ±15yo). At the last cardiac ultrasound, pituitary magnetic resonance imaging (MRI), spine MRI, testicular ultrasound, mammography performed at 40±15yo, 37.9±14.3yo, 46±12yo, 35±13yo and 48±12yo, no patient had cardiac myxoma, pituitary adenoma, schwannoma, testicular calcifying tumor or breast myxoma. Overall, 52% of the relatives did not have any manifestations of the disease. Penetrance of the disease is 65%. Conclusion: The phenotype of patients carrying the c.709(-7-2)del PRKAR1A mutation is restricted to PPNAD, lentigines, fluctuating somatotroph anomalies and thyroid tumors. Follow-up of these patients should also be individualized from other CNC patients. Imaging, especially repeated cardiac ultrasound may not be needed to follow these patients The results of this real life study will be useful to elaborate further recommendation for follow-up of CNC patients.
MON-903 Sporadic Phaeochromocytoma, Pancreatic Neuroendocrine Tumour and a Sacral Hibernoma: A Case Report
Authors: Pandher Ravind Singh , Hibbert Emily
Published: May 2020

Most phaeochromocytomas and pancreatic neuroendocrine tumours are sporadic in nature however the presence of multiple neuroendocrine tumours raises the suspicion of a hereditary endocrinopathy. Hibernomas, benign tumours that morphologically resemble brown fat, do not possess a clear aetiology and a link with other neuroendocrine tumours remains unclear. We report an unusual case of a concurrent sporadic phaeochromocytoma, pancreatic neuroendocrine tumour and a sacral hibernoma. A 61 year old female presented with a 3 month history of abdominal pain which led to the discovery of a lesion in her right adrenal gland and a soft tissue mass at the pancreatic tail on a CT Abdomen. The adrenal lesion was biochemically suggestive of a phaeochromocytoma (plasma normetanephrine 4930 pmol/L, plasma 3-methoxytyramine 580 pmol/L, urinary noradrenaline 5564 pmol/day, urinary dopamine 4720 nmol/day). A 68Ga-DOTATATE-PET-CT scan revealed DOTATATE avid lesions in the right adrenal gland, tail of pancreas and right sacral ala. Following preoperative medical therapy, the patient underwent a right adrenalectomy and a resection of the distal pancreatic lesion.Histopathology confirmed a phaeochromocytoma with no conscipicouous mitotic activity, and the pancreatic tail lesion was consistent with a well-differentiated neuroendocrine tumour (NET) (Ki-67 score <3%). Following normalisation of the serum catecholamines, a biopsy of the sacral lesion was undertaken, which returned positive for a hibernoma. Genetic testing revealed no identifiable genetic mutations.This case reports the synchronous presence of a phaeochromocytoma, pancreatic NET and sacral hibernoma with no identifiable genetic mutation. To date, the association between hibernomas and neuroendocrine tumours has not been fully established, but a few case reports suggest a possible association between MEN1 and hibernomas.
MON-394 Vitamin D Levels and Functional Recovery Following Hip Fracture
Authors: Mohan Sneha , Holte Pamela K , Yuan Brandon J , Sems Stephen A , Kearns Ann E
Published: May 2020

Background: Vitamin D deficiency is common in patients presenting with low energy hip fractures. The relationship between Vitamin D levels at the time of a fracture with long term functional outcomes has not been studied. Identifying a benefit to recovery with adequate vitamin D would support supplementation in elderly patients at risk for hip fracture.

Methods: A retrospective cohort of patients >/= 50 years, who were treated surgically for low energy hip fracture between July 1 2016 and June 30 2018 were identified. The correlation between Vitamin D levels and functional recovery, assessed using the time up and go (TUG) test, survival at 3 months and 1 year, and readmission within 3 months was examined. The Charlson comorbidity index (CCI) at baseline was also assessed.

Results: A total of 216 patients were treated for a hip fracture of which 174 were included with measured baseline Vitamin D levels. A majority were female (112, 64.4%), mean age 79.6 years (+/-11.9), mean Vitamin D level 28.2 ng/ml (+/- 12.4) and mean CCI 5.9 (+/- 2.5). Vitamin D <20 ng/ml was seen in 39 (22.4%) patients and all received appropriate supplementation. 39 (22.4%) individuals died within a year of surgery, among whom 17 (43.6% of 39) passed away within 3 months. 36 (20.7%) were readmitted within 3 months of surgery and 14 (8%) sustained a second fracture within a year. The correlation of Vitamin D levels, taken as a continuous variable, to outcomes, was analyzed using logistic regression. Although not significant, higher Vitamin D was found to be protective against death within 3 months (OR=0.995, p=0.8), but actually increased the odds of death within 1 year (OR=1.008, p=0.62), readmission within 3 months (OR=1.001, p=0.96), second fracture within 1 year (OR=1.017, p=0.33) and failure to recover (OR=1.002, 0.86). After adjusting for age, gender and CCI, Vitamin D levels were non-significantly inversely associated with both TUG 1 and TUG2, with every 1 unit higher Vitamin D associated with a TUG lowered by 0.15 seconds, p=0.42 and 0.44. Vitamin D was poorly correlated to CCI with correlation coefficient of 0.02, p = 0.71.

Conclusions: Our results indicate that Vitamin D levels at the time of a hip fracture do not correlate with patients’ functional outcomes. It is possible that replacing vitamin D eliminated the possible negative impact on functional recovery.
SAT-267 Pregnancy in Acromegaly: Report of Five Cases
Authors: Burcea Iulia Florentina , Dusceac Roxana , Baciu Ionela , Capatina Cristina , Niculescu Dan , Poiana Catalina
Published: May 2020

Introduction: In acromegaly, there are changes in growth hormone (GH), insulin-like growth factor-1 (IGF-1) and insulin, hormones very important in pregnancy as well. Despite novel treatments, pregnancy in acromegaly is uncommon, remaining a challenge for clinicians.

We report seven pregnancies in five women with acromegaly.

Clinical Cases: Five acromegalic patients (17 – 35 years-old) underwent seven pregnancies. All patients had macroadenoma: four were submitted to non-curative neurosurgery and two of them had gamma-knife radiosurgery. One patient had medical treatment prior to curative transsphenoidal surgery (TSS).

One patient being treated with estroprogestative for hypogonadism had a spontaneous pregnancy; three others had pregnancy just before biochemical diagnosis of acromegaly, one of them had also a spontaneous abortion and another successful pregnancy during treatment with somatostatin receptor ligand (SRL); the last patient become pregnant during treatment with SRL, prior to TSS.

Monitoring was made with IGF-1, GH (assay with no distinction of pituitary GH versus placental GH), prolactin (PRL) and visual field; pituitary imaging was performed after pregnancies in all.

All women conceived naturally, two being on treatment with SRL (discontinued after confirmation of pregnancy). No treatment for acromegaly was administered before delivery. All patients had physiologic pregnancies, delivered full-term healthy babies, no malformations or metabolic disruptions; one did not breast-feed; another one had a spontaneous abortion 2 days after confirmation of pregnancy.

No patient developed either hypertension, pre-eclampsia or gestational diabetes.

In three cases, the clinical suspicion of acromegaly had risen during pregnancy and the diagnosis was made 1 year after delivery. The one with three pregnancies had controlled secretion of GH on Lanreotide and GH and IGF-1 levels remained stable during pregnancy.

The woman with gonadotroph deficiency after TSS and GK and substitutive therapy had a decrease in IGF-1 during pregnancy (45 %), which after delivery returned pathologically to before pregnancy values; GH levels remained stable.

The last patient, who became pregnant with uncontrolled acromegaly on Pasireotide, had increased, but stable GH and IGF-1 (2 X upper limit of normal) before, during and after pregnancy. TSS performed 3 years after delivery cured the disease.

Conclusion: From our experience, patients with acromegaly may have normal babies, even in patients with uncontrolled hypersecretion and lack of medical treatment during pregnancy. The consensus is, however, that there is no indication to use medication to control GH hypersecretion or tumor size in acromegaly patients during pregnancy (1).

Reference: (1) Muhammad A, Neggers SJ, van der Lely AJ. Pregnancy andacromegaly. Pituitary. 2017;20(1):179–184. doi:10.1007/s11102-016-0740-3
MON-078 WFS1 Related Disorder in A 4-Month Old Girl
Authors: Kleanthous Kleanthis , Manolakos Emmanouil , Dermitzaki Eleni , Fretzayas Andreas , Urano Fumihiko , Papadimitriou Dimitrios T
Published: May 2020

Background: Idiopathic early-onset central diabetes insipidus (CDI) may be due to mutations of arginine vasopressin-neurophysin II (AVP-NPII (AVP)) or wolframin (WFS1/2) genes (1).

Clinical Case: A 4-month old girl presented to our pediatric endocrinology clinic due to severe polydipsia-polyphagia and polyuria. Plasma and urine glucose and HbA1c were normal and 24h monitoring of urinary output was elevated (4.2ml/kg/h). We proceeded to a modified 5-h water deprivation test followed by 0.1 mcg DDAVP IM. Results were compatible with partial central DI: at 5-hrs weight loss 5%, urine osmolality 155 from 111 at 0΄and 355 mOsm/kg 2hrs after DDAVP administration.

Pituitary MRI was normal with presence of posterior pituitary bright spot and normal pituitary stalk.

We initiated therapy with oral desmopressin acetate titrated at the dose of 70mcg x 3/day under close clinical and biochemical surveillance. Hyponatremia, with high natriuresis >100 mmol/L and elevated BNP occurred the 3rd day. Fludrocortisone 100 mcg x 2/day controlled natriuresis and supplemental oral NaCl 15% 15ml/day was needed to restore normal electrolytes (2).

Marked catch-up growth was observed already at 1 month for height, weight and head circumference.

Methods: Whole exome sequencing was performed targeted to a gene panel related to DI, containing AVP gene, WFS1/2 genes and AVPR2/AQP2 genes.

Result: Two heterozygous variants were revealed: WFS1:NM_001145853:exon8:c. G997A:p.V333I,WFS1:NM_006005:exon8:c.G997A:p.V333I and WFS1:NM_00114585 3:exon8:c.G1832A:p.R611H,WFS1:NM_006005:exon8:c.G1832A:p.R611H reported as possibly damaging in 1/6 and 4/6 prediction programs respectively. These variants will be checked in both parents to confirm the presumed compound heterozygosity pattern in the child.

Conclusion: We present a 4-month old girl with two heterozygous variants of WFS1 gene which may cause early-onset central diabetes insipidus and possibly a WFS1 related disorder (1).

Reference:

(1) Perrotta S et al. Early-onset central diabetes insipidus is associated with de novo arginine vasopressin-neurophysin II or Wolfram syndrome 1 gene mutations. Eur J Endocrinol. 2015 Apr;172(4):461-72

(2) Papadimitriou DT, Spiteri A, Attilakos A, Papadimitriou A. Cerebral Salt Wasting Complicated by Central Diabetes Insipidus and Growth Hormone Deficiency. Indian J Pediatr. 2018 Jul;85(7):580-581
SUN-523 Thyroid Storm: A Rare Presentation of HCG Producing Metastatic Choriocarcinoma
Authors: Chivukula Krishna Karthik , Toro-Tobón David , Motazedi Banafsheh , Goyal Rachna Manju
Published: May 2020

Background: The beta subunit of human Chorionic Gonadotropin (hCG) and TSH are very similar and hCG is known to weakly bind the TSH receptor. hCG induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ-cell tumors and usually presents with subclinical thyrotoxicosis. We present a noteworthy case of thyroid storm in a patient with hCG producing testicular Choriocarcinoma.

Clinical case: A 19-year-old Hispanic man presented to an outside emergency department (ED) with one day of abdominal pain, nausea, recurrent emesis and subjective fever. He had presented to the same ED 9 days prior with similar symptoms which prompted contrasted CT Abdomen/Pelvis demonstrating hepatic masses and a large right testicular mass, suspicious for primary testicular malignancy. On return evaluation, he was noted to have tachycardia with HR 165, mild scleral icterus, tenderness to palpation of right upper quadrant, abdominal pain and a right scrotal mass (5x5 cm). CBC revealed; WBC 12.0 k/uL (n: 4-10.8), AST: 428 u/L (n: 3-34); ALT: 176 u/L (n: 15-41); total bilirubin: 6.3 mg/dL (n: 0.2-1.3), TSH <0.005 uIU/mL (n: 0.4-4.0) and FT4 5.02 ng/dL (n: 0.7-1.4). Clinical scenario was consistent with thyrotoxicosis concerning for thyroid storm (Burch-Wartofsky Point Scale: 50) requiring intensive care for which he was transferred to our institution. Thyroid US revealed increased thyroid vascularity without nodularity. Laboratory workup revealed negative TG Ab, Anti-TPO Ab, TRAb, and TSIG. Conversely, TBG was elevated at 31.2 mcg/ml (n: 13-30). Initial hCG level was obtained as 6,074. After re-testing with dilution was specifically requested, initial hCG was corrected to 6,760,713. Oncologic workup confirmed diagnosis of hCG producing testicular choriocarcinoma with liver and lung metastases. On admission, he was started on oral methimazole and propranolol as well as intravenous steroids which led to marked symptomatic improvement and normalization of FT4 to 1.37 allowing for discontinuation of antithyroid medication on 7th day of hospitalization. He completed 1 cycle of cisplatin/etoposide and experienced marked reduction of his hCG level to 951,460 which correlated with improvement of his TFTs and resolution of his hyperthyroid symptoms.

Conclusion:

A low threshold of suspicion should be maintained for the possibility of hyperthyroidism in patients with suspected testicular choriocarcinoma, particularly in the context of recent iodinated contrast imaging. If the clinical picture does not support a primary etiology of hyperthyroidism and hCG is not concordantly elevated, re-assessment of hCG by dilution should be considered as hCG assay is also subject to prozone (hook) effect. Hyperthyroidism should be actively managed and closely monitored as response to treatment can be rapid.
SUN-479 Metastatic Renal Cell Carcinoma (RCC) to the Thyroid: Case Report and Clinical Lesson
Authors: Reddy Sreedevi Singidi , Reddy Nisha
Published: May 2020

Background: Metastatic neoplasms to the thyroid gland are rare and have been observed more in autopsy series than in clinical series.

Case: A 71-year old woman presented for thyroid nodule evaluation which was incidentally noted on CT/PET scan. She was diagnosed with renal cell carcinoma (RCC) stage IV (6.4 cm, left nephrectomy) 4 months prior. She had right hemi-thyroidectomy 30 years prior for a benign nodule. She was clinically and biochemically euthyroid with dysphagia and hoarseness in her voice. Thyroid u/s revealed multiple nodules in the left lobe with a dominant 3.6 x 2.9 x 3.6 cm solid, heterogeneous nodule with grade 3 hypervascularity. History positive for 1 cm right renal mass and multiple pulmonary nodules increasing in size thought to be consistent with metastases. The FNA of the dominant nodule was indeterminate, Bethesda III (AUS), GSC suspicious (Affirma, 50% ROM) with negative malignancy classifiers. Patient underwent completion thyroidectomy, and surgical path was consistent multifocal clear cell renal cell carcinoma (CRCC) with the largest focus of 3 cm based on clear cell features and strong positivity for stains: CK OSCAR, RCC, PAX-8 & CD-10. Patient is currently on Pazopanib post thyroid surgery for 18 months, and is stable with no further increase in the size of lung nodules or right renal mass and negative serial PET scans.

Clinical lesson: CRCC represents 3-4% of all adult malignancies and 85% of all primary renal tumors. In clinical series, CRCC is the most frequent source of thyroid metastases and represents 12-34% of all secondary thyroid tumors. About 17% of patients with CRCC have metastatic disease at diagnosis. Metastases can be synchronous or metachronous to the primary tumor. Latency from nephrectomy to diagnosis of thyroid mets varies from 2 months-21.9 years. Metastases can be solitary (more common), multiple or diffuse. Radiological findings typically reveal hypoechoic and vascularized mass on ultrasound and cold on thyroid scan. Metastases to thyroid can pose diagnostic problem and be a source of confusion in cytology interpretation. Metastatic CRCC can simulate morphologically primary thyroid neoplasm such as Hurthle cell neoplasm or thyroid carcinomas with clear cell changes. Metastatic carcinoma within the thyroid gland is negative for thyroglobulin, TTF-1, calcitonin unlike primary thyroid cancer. CRCC is usually positive for periodic acid-Schiff and Oil red O, vimentin, and CD10. The mean survival in patients with CRCC who had thyroidectomy alone or with adjuvant treatment was 3 years.

Conclusion: Thyroid metastases should be considered in patients with thyroid nodules and positive history of RCC. The preoperative distinction between primary and secondary tumors is difficult. Immunohistochemistry is a useful method for the evaluation of patients with suspected thyroid nodules.
SUN-663 Dietary Coconut Oil Mitigates Features of Metabolic Syndrome in Obese Females
Authors: Skenandore Cassandra , Ali Anisah , Gil Lesly , Schwartz Rani , Goblet Camille , Kothmann Kadden , Browning Luke , Newell-Fugate Anne Elizabeth
Published: May 2020

Forty percent of American women are obese and at risk for metabolic syndrome. Coconut oil alters circulating lipid levels and improves glucose homeostasis in lean individuals, yet, whether it can exert these same beneficial effects on cardiometabolic health in obese individuals is unknown. We hypothesized that female pigs fed a high fat diet with 5% coconut oil would have improvements in features of metabolic syndrome (i.e., dyslipidemia) compared to female mini-pigs fed a high fat diet with 5% lard. We fed female pigs 2200 kcal of a control (n=6), 5000 kcal of a lard high fat (WSD; n=5), or 5000 kcal of a coconut oil high fat (COC; n=6) diet for a total of 9 estrous cycles (~ 7.5 months). Fasting blood was collected at the 1st, 7th (C 7), and 9th (C 9) estrous cycle. After C 7, an intravenous glucose tolerance test (IVGTT) was performed. Weights and morphometric measurements were taken weekly. Tissue was collected for histology at C 9. WSD females (15.14 ± 1.85 mg/dL) had a greater increase in fasting glucose as compared to COC (3.51 ± 4.31 mg/dL) and C females (0.45 ± 3.32 mg/dL; p<0.05). COC females tended to be more glucose tolerant (p=0.07) and had lower serum insulin concentrations in response to a glucose bolus (p<0.001) than WSD females. COC (82.6 ± 1.1 kg) and WSD females (85.4 ± 1.0 kg) weighed more (C: 61.9 ± 1.1 kg; p<0.0001) and had larger abdominal circumferences (COC: 122.4 ± 0.8 cm; WSD: 117.4 ± 1.0 cm) than control females (102.6 ± 1.0 cm; p<0.0001). WSD females were the most dyslipidemic, with the greatest increase in triglycerides (C: 0.33 ± 1.5 mg/dL; COC: 7.71 ± 3.0 mg/dL; WSD: 17.25 ± 3.0 mg/dL; p=0.03) and HDL:cholesterol (C: 3.44 ± 0.22; COC: 5.00 ± 0.36; WSD: 6.00 ± 0.42; p=0.05) as compared control and COC females. COC females had increased plasma docosahexaenoic acid (C: -0.128 ± 0.291; COC: 0.262 ± 0.260; WSD: -0.732 ± 0.274; p<0.01) and decreased arachidonic acid (C: 2.418 ± 0.744; COC: -4.561 ± 0.666; WSD: -2.068 ± 0.702; p<0.01). COC females (131.26 ± 10.0 μm) had a decreased average omental adipocyte diameter as compared to WSD females (160.06 ± 10.31 μm; p=0.05). COC females (7.3 ± 0.80 %) had less hepatic lipid accumulation as measured by oil red o stain than WSD females (9.2 ± 1.1 %; p=0.05). These data demonstrate that small amounts of dietary coconut oil, even as a part of a high fat diet, can mitigate features of metabolic syndrome and decrease hepatic and visceral adipose tissue lipid accumulation in obese females.
SAT-684 A Deadly Triad: Coexistence of Acute Pancreatitis, Hypertryglyceridemia and Diabetic Ketoacidosis
Authors: Torres Torres Marina T , Padilla Rodriguez Kimberly C , Vergne-Santiago Norma , Garcia Michelle Marie Mangual
Published: May 2020

The coexistence of diabetic ketoacidosis (DKA), hypertriglyceridemia and acute pancreatitis (AP) represent a complex phenomenon described as the enigmatic triad. The exact initial culprit and pathophysiologic mechanism of this chain of events are still unclear posing a challenge in management. DKA may lead to glucose and lipid metabolism dysregulation which can result in hypertriglyceridemia leading to AP. On the other hand, hypertriglyceridemia may induce AP which may decompensate diabetes and lead to DKA. In both scenarios, this triad results in an uncommon clinical presentation with up to 80% mortality rate. Most frequently reported in children, this entity accounts for only a handful of cases reported in the literature.

Case of an obese, non alcoholic 57 year old male without history of systemic illness who visits the emergency room due to mid-upper abdominal pain for the past day. Pain radiates to the back, worsens upon laying flat, and is associated with bloating and nausea. He denies previous similar episodes, vomiting, fever or bowel habit changes. Laboratory workup revealed lipidemic sample with hyperglycemia, metabolic acidosis, positive serum ketones, and normal amylase and lipase. Lipid panel revealed hypertriglyceridemia at 6,260 mg/dL (35-150). Glycated hemoglobin at 14.7%. Abdominal computed tomography showed peripancreatic inflammation consistent with pancreatitis. Given clinical and imaging criteria the diagnosis of severe hypertriglyceridemia induced AP and DKA were made. The patient was admitted to ICU and treated with intravenous insulin drip and supportive management. Resolution of DKA and successful decrease in triglycerides to less than 500 mg/dL was achieved by the third day of admission. After six days, the patient was discharged home with insulin and lipid lowering regimens.

This case demonstrates an extremely rare initial presentation of diabetes mellitus. This triad is the result of a toxic chain of events that may be lethal if not promptly identified. This case makes an exemplary lesson as to always take under consideration atypical etiologies to potentially life threatening conditions and also remarks that while uncommon, pancreatitis with normal pancreatic enzymes is a possible phenomenon. Even though false negative amylase has been associated with hypertriglyceridemia induced AP, only a few cases with negative lipase have been described. While no definite explanation has been yet discovered, negative lipase may be explained by early acinar cell apoptosis in AP. More research efforts are necessary in order to improve early diagnosis, treatment, and mortality rate for this rare but potentially deadly triad and to better understand the mechanisms underlying AP and the role that digestive enzymes play.
SUN-184 Pseudohypoaldosteronism Presenting with Salt Wasting Crisis
Authors: Babar Ghufran S
Published: May 2020

Pseudohypoaldosteronism (PHA) is due to end organ resistance to mineralocorticoids. It is usually inherited in an autosomal recessive or autosomal dominant pattern, and rarely can a result of the mutation de novo. Zennaro MC, Hubert EL, Fernandes-Rosa FL. Aldosterone resistance: structural and functional considerations and new perspectives. Mol Cell Endocrinol. 2012;350:206-15.10.1016/j.mce.2011.04.023[Crossref], [PubMed], [Web of Science ®] It can be sub-classified into two forms PHA type 1 A involving the kidneys or PHA-1 B which effects multiple organs. PHA type 2 (Gordon syndrome) presents with hyperkalemia and hypertension. Case: Our patient is a 5 week old male who admitted for significant electrolyte abnormalities. He was followed by PCP for failure to thrive. The child was referred to ED with increased difficulty in feeding, lethargy and episodes of emesis. In the ED, the child was in a compensated shock and had a low normal BP: 76/35, HR: 169/min and fast breathing R/R: 80/minute and afebrile. P.E: showed signs of dehydration. Lab work showed: Na: 110 mEq/L, K: 9.3 mEq/L, low Chloride and Ca: 11.1 mEq/L. Endocrinology recommended IVF supplementation with 2 x NS bolus followed by IVF’s at 1.5 times maintenance (D5 + NS), along with administration of Florinef 0.2 mg suspecting CAH. Renin, 17-OHP, random cortisol level and thyroid hormone levels were ordered. Results showed: TSH of 5.30 mcIU/mL and Free T4 of 2.2 ng/dL. Cortisol: 20.5 mcg/dL. He was subsequently admitted to PICU. Septic work-up was negative. He became hemodynamically stable after hydration and did not require the stress dose of hydrocortisone. Repeat Na: 133 mEq/L, K: 4.7 mEq/L, Cl: 102 mEq/L and Glucose: 90 mg/dL. ACTH stimulation test for CAH evaluation was performed, stimulated 17OHP: 88 ng/dl, cortisol: 27.1 mcg/d and normal DOC. Elevated Aldosterone: 632 ng/dl (5-80) and renin level: 351 (6.5-86). A diagnosis of PHA was made and florinef was stopped and the child was started on NaCl supplementation which normalized the electrolytes. Genetic testing was negative for NR3C2, CUL3, KLHL3, SCNN1A, SCNN1B, SCNN1G, WNK4 and showed that the patient is a heterozygous for a variant of unknown significance, c.6276T>A (p.Ser2092Arg) in the WNK1 gene. However, the patient did not have hypertension and urine electrolytes were also normal did not show signs of PHA 2. Conclusion: PHA can present with severe salt wasting crisis. It can be diagnosed clinically. The relationship of mutation and phenotype can be elusive. Course was uncomplicated and he was discharged from the PICU in 6 days. Sodium doses were titrated based on serum levels with eventual dose of 22.5mEq/kg/day and sodium level was 139 mEq/L.