bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-203 Hyponatremia and Hyperkalemia in a Child with Chylothorax: Is This Adrenal Insufficiency?
Authors: Ovando Dennerd , Iregui Adriana Carrillo , Christin Nicole M 
Published: May 2020

Abstract
Hyponatremia and Hyperkalemia in a child with chylothorax: Is this adrenal insufficiency?
Context: Chylothoraces are relatively rare within the pediatric population. Drainage of a chylothorax can lead to potentially serious complications including electrolyte imbalances and protein loss. The literature on hyponatremia and hyperkalemia developing after a chylothorax drainage is sparse. We report a case of electrolyte derangements after a chylothorax drainage in a pediatric patient. Repeated drainage of a large-volume chylothorax without adequate fluid replacement may lead to electrolyte imbalances that in our case mimicked adrenal insufficiency. Early identification and correct fluid replacement can avoid unnecessary complications of a chylothorax.
Case Description: A 2-year-old female with history of congenital left pulmonary lymphangectasia and subsequent pleural effusion was admitted to a pediatric hospital for persistent tachycardia after an outpatient elective chest MRI. A chest tube was placed to drain the effusion with large volume output was noted over the first day (1200 cc/24 hours). Further chemical analysis determined the effusion to be consistent with a chylothorax. Blood work done after chest tube placement demonstrated severe hyponatremia and hyperkalemia. Additionally, the patient was noted to be irritable. Both lab and clinical findings raised concern for possible underlying adrenal insufficiency, and further work-up (i.e. cortisol level, ACTH level) was sent. The patient was started on stress-dose steroids. ACTH and cortisol levels resulted normal. Steroids were subsequently discontinued. The patient’s chest tube output was slowly replaced with normal saline with noted improvement in both lab and clinical findings.
Conclusion: Although not well documented in pediatric literature, hyponatremia and hyperkalemia are complications of large-volume drainage of chylothoraces without proper fluid replacement. The subsequent lab findings could be consistent with adrenal insufficiency, however a full clinical picture along with a cortisol and an ACTH level can help differentiate etiologies.
SAT-236 Unusual Presentation of a Stable Pituitary Macroadenoma with Pituitary Apoplexy Causing SIADH and Pan-hypopituitarism
Authors: El-Zein Louna S , Abushanab Dania , Chaker Bayan 
Published: May 2020

Abstract
We are reporting a case of SIADH hyponatremia and pan-hypopituitarism in an otherwise stable appearing non-functional pituitary macroadenoma on MRI that suddenly developed apoplexy.
Patient is a 52-year-old hispanic male with a history of a pituitary adenoma diagnosed initially on 06/2017 during MRI head for chronic headaches. MRI Pituitary on 07/2018 showed “well-circumscribed lesion” measuring approximately 12.7 x 14.8 x 13.4 mm in AP. Hormonal work up was normal in 06/2017, 01/2018, and 07/2018. In 07/2018 labs showed: IGF-1 247 ng/mL (65–222), ACTH 28 pg/mL (7–69), random cortisol 8.58 microg/dL (3.09–22.4), TSH 2.3 mIU/mL (0.4–5.5), fT4 1.06 ng/dL (0.8–1.8), LH 4.6 mIU/mL (0.98–79.7), FSH 6.2 MIU/mL (1–18), prolactin 2.92 ng/mL (2.1–24), and testosterone 310 ng/dL (87–814). Oral glucose tolerance test was done and showed: GH was 0.34 ng/mL at baseline and 1.01 ng/mL after 75 g oral glucose (equivocal result). Repeat IgF1 was normal after that.
Subsequently, patient was admitted on 09/24/2018 with severe headaches, nausea, vomiting, polyuria, and polydipsia. He was hypotensive and tachycardic and was found to be hyponatremic with a Na of 124, lowest at 119 where hypertonic saline was given at that point. Urine output was 1.5 L in 24 hours while he was on an 0.8 L fluid restriction, and then 6 L the following day while he was on 1.5 L fluid restriction, serum osmolality was 251, urine osmolality was 1003, urine specific gravity was &gt;1.030. Nephrology agreed to the diagnosis of SIADH.
Blood work on 09/24 showed: random cortisol 0.67 microg/dL, TSH 0.19 mIU/mL, free T4: 0.63 ng/dL, ACTH 11 pg/mL, LH 2.4 mIU/mL, FSH 4.7 MIU/mL, testosterone 13 ng/dl. Patient was started on Levothyroxine 125 mcg and hydrocortisone stress dose. MRI brain was done and showed a pituitary macro-adenoma, measuring approximately 14 x 11 x 11 mm with no significant change in size since 6/30/2017, without optic nerve compression, no hemorrhage was mentioned. Work up for other causes of panhypopituitarism, i.e. hemochromatosis was done and was negative: Ferritin: 258 ng/mL (22–322). CT abdomen and pelvis was also done and showed normal adrenal glands. We thought about granulomatous infiltrative diseases like sarcoidosis since 1–25 (OH) vitamin D was high at 120 pg/mL (19.9–79.3). CT neck and chest was done but was negative for sarcoidosis or lymphadenopathy. Patient was seen outpatient by neurosurgery in 1/2019 and a repeat MRI was done which reported resolution of cystic and blood material from a pituitary adenoma, and per neurosurgery there is resolution of a pituitary cystic adenoma with apoplexy that now looks like a partial empty sella. Patient currently continues to be pan-hypopituitary requiring hydrocortisone, levothyroxine and testosterone replacement. SIADH has resolved.
An otherwise non-functioning stable pituitary macroadenoma on MRI, can suddenly present as symptomatic apoplexy with SIADH and pan-hypopituitarism.
SUN-504 A Case of T3 Thyrotoxicosis
Authors: Peloquin Isabelle Daneault , St-Jean Matthieu 
Published: May 2020

Abstract
Clinical vignette ENDOCRINE SOCIETY 2020
Title: A case of T3 thyrotoxicosis induced by a dietary supplement.
A 24 yo man consulted for a 2 weeks history of diaphoresis, fatigue, insomnia, palpitations and headache associated with a 20 pounds lost. The patient didn’t have a goiter or any signs of orbitopathy.
The results revealed a free T3 level of 45.8 pmol/L upon arrival (normal (N) 3.4- 6.8 pmol/L), free T4 level of 6.4 pmol/L (N 11.0–22.0 pmol/L) and TSH level less than 0.005 mUI/L (N: 0.35 to 3.50 mUI/L). Facing those results, a complete review of the patient medication and natural product consumption was done. The patient revealed that he was using, since a month, a vegetable extracts nutritional supplement that didn’t included iodine. He was asked to stop the nutritional supplement and propranolol 10 mg twice daily was prescribed. Thyroid function tests were done 3 days after. The results demonstrate a fT3 level of 4.6 pmol/L, a fT4 level of 5.6 pmol/L and a TSH that still suppressed. A thyroid scintigraphy was performed 7 days later and showed a homogeneous uptake of 18.5% (N 7.0% – 35.0%). We saw the patient 2 weeks later and we ordered another thyroid function test with TSH receptor antibodies, TPO antibodies and thyroglobulin. The results were the following: fT3 of 5.1 pmol/L, fT4 of 12.1 pmol/L, TSH of 2.31 mUI/L, thyroglobulin of 19.8 ug/L (N: 1.4 – 78) and normal levels of antibodies against TPO and TSH receptors. To confirm the contamination of the nutritional supplement by fT3 we used a plasma pool of normal patients in which we measured thyroid function tests at baseline and after we have added the nutritional supplement powder to reflect the dose suggested by the manufacturer. The results showed that fT3 level increased by 36.5%, fT4 by 11.2% and TSH didn’t changed. The powder was then analyzed by an external laboratory that wasn’t able to demonstrate the presence of fT3 nor fT4. The two diagnostic possibility facing those results were that the powder induced an interference with immunoassay used to measure fT3 and fT4 but not TSH or thyrotoxicosis induced by the nutritional supplement with limitation in the technique that tried to identify fT3 in the powder. Given the presentation of the patient, we are convinced that this case represents a thyrotoxicosis induced by a nutritional supplement.
In conclusion, Graves’ disease is responsible for 60–80% of the cases of hyperthyroidism. However, there are few cases reports of thyrotoxicosis induced by nutritional supplement1,2, but some studies demonstrate the presence of thyroid hormone in significant amounts in some commercially available health supplements3. This case highlights the importance of verifying exposition to medications and natural products when confronted to cases of thyrotoxicosis.
1.Regina A et al. MMWR Morb Mortal Wkly Rep. 2016
2. Panikkath R et al. Am J Ther. 2014
3. Kang GY et al. Thyroid. 2013
SAT-283 Generation of a Long-Acting Human Growth Hormone Receptor Antagonist by Site-Specific Pegylation
Authors: Wang Yue , Langley Ries J , Tamshen Kyle , Maynard Heather D , Jamieson Stephen M F , Perry Jo K 
Published: May 2020

Abstract
Growth hormone (GH) is a peptide hormone that mediates actions through binding to a cell surface GH receptor (GHR), activating key signalling pathways including the JAK/STAT pathway. Excess GH secretion leads to acromegaly and tumoral expression has been implicated in cancer progression, suggesting that GH is also a potential target for anticancer therapy. Pegvisomant is the only GHR antagonist approved for clinical use. This antagonist is a PEGylated form of a mutated GH (B2036) that binds and blocks the receptor. Conjugation to polyethylene glycol (PEG) at multiple amine residues reduces in vitro bioactivity but extends the serum half-life resulting in improved in vivo bioactivity. We investigated whether we could generate a long-acting PEGylated GHR antagonist through site-specific conjugation of PEG. A codon optimised GHR antagonist, with an introduced free cysteine residue at amino acid site 144 (S144C), was generated by gene synthesis and recombinantly engineered by gene fusion with thioredoxin. Recombinant protein was expressed in E. coli and purified using a series of chromatographic methods. Antagonists were PEGylated using cysteine-specific conjugation chemistry. In vitro activity was determined using a Ba/F3-GHR viability assay, and in vivo pharmacokinetic and bioactivity was determined in mice. Fusion to thioredoxin was found to improve soluble protein expression at 30℃, resulting in dramatically increased yield. After a series of purification steps, including Ni-NTA, 3C protease cleavage and ion-exchange chromatography, a single band with a molecular mass of 22 kDa was observed by SDS-PAGE analysis. The recombinant antagonist was conjugated to 20 kDa or 30 kDa-PEG at amino acid site S144C. After purification, a single band with an effective molecular size of approximately 60 kDa (PEG-20kDa conjugate) or 70 kDa (PEG-30kDa conjugate) was observed by SDS-PAGE analysis. The unconjugated antagonist inhibited the proliferation of Ba/F3-GHR cells in a dose-dependent manner with a half maximal inhibitory concentration (IC50) of 10.1 ± 2.5 nM. Following PEGylation and purification, the PEG-20kDa and PEG-30kDa conjugates retained high in vitro bioactivity with an IC50 of 66.2 ± 3.8 nM and 106.1 ± 7.1 nM, respectively. Pharmacokinetic analysis demonstrated that PEGylation increased the serum half-life to approximately 15 hours in mice. Subcutaneous administration of the PEG-30kDa conjugate (10 mg/kg/day) reduced serum IGF-I levels in mice. In conclusion, we have generated a novel long-acting human GHR antagonist conjugate by introducing a free cysteine at a non-essential site of the antagonist and targeted attachment of PEG.
SAT-308 Effect of Silibinin on ACTH Synthesis and Secretion in Human Adenomatous Corticotropes in Vitro
Authors: Cassarino Maria Francesca , Sesta Antonella , Libera Laura , Bardelli Donatella , Losa Marco , Lasio Giovanni , Giraldi Francesca Pecori 
Published: May 2020

Abstract
Silibinin, a milk thistle extract with known hepatoprotective effects, has recently been shown to act upon tumoral corticotropes and revert the Cushingoid phenotype in an allograft mouse model (Riebold et al 2015). Silbinin is known to inhibit HSP90 -a chaperone to the glucocorticoid receptor- thereby restoring sensitivity to glucocorticoid negative feedback in tumoral corticotropes. Aim of the present study was to assess the effect of silibinin on ACTH synthesis and secretion by human corticotrope adenomas in vitro. Methods: Eight human ACTH-secreting pituitary adenomas were collected during surgery and established in culture as per our protocol (Pecori Giraldi et al 2011). Specimens were treated with 10 - 50 µM silibinin for up to 72 hours. ACTH medium levels were measured by Elisa; POMC expression was assessed by RT-PCR (Cassarino et al 2017). Results. Silibinin reduced spontaneous ACTH secretion to a variable extent in individual adenomas: from 32 to 79% of baseline at 4h, and 54 - 85 % of baseline at 48 and 72h. Silibinin was also effective in reinstating or enhancing sensitivity to steroid negative feedback: ACTH decreases during 10–50 µM silibinin incubation ranged from 10 to 63% of dexamethasone-treated wells at 4 hours, 70 -80% at 48 hours and 36 to 80% at 72 hours, indicating long-lasting effect on glucocorticoid sensitivity. Silibinin induced a variable decrease in POMC expression, both as regards expression in control and dexamethasone-treated wells; some specimens exhibited a marked sensitivity to the inhibitory effect, with POMC expression decreasing to less than 50% of control. Conclusions:, this data suggests that silibinin can inhibit ACTH secretion and POMC synthesis and restore sensitivity to negative glucocorticoid feedback. References: Cassarino et al (2017) Endocrine55: 853–860. Pecori Giraldi et al (2011) Journal of Neuroendocrinology23:1214–21. Riebold et al (2015) Nature Medicine21:276–280.
SUN-117 Growth Hormone-Releasing Hormone (GHRH) Deficiency Promotes Inflammation Associated Carcinogenesis
Authors: Recinella, PharmD Lucia , Leone Sheila , Chiavaroli, PharmD Annalisa , Ferrante, PharmD Claudio , Orlando, PharmD Giustino , Salvatori Roberto , Brunetti Luigi 
Published: May 2020

Abstract
The somatotropic axis, in addition to its well-known metabolic and endocrine effects, plays a pivotal role in modulation of inflammation. Additionally, GH-releasing hormone (GHRH) has been involved in the regulation of the growth of various human tumors. In this work, we aimed to investigate the consequences of GHRH and GH deficiency on the development of inflammation-associated colon carcinogenesis in a mouse model of isolated GH deficiency due to generalized ablation of the GHRH gene [GHRH knock out (GHRHKO)]. Homozygous GHRHKO (-/-) male mice and wild type (C57/BL6, +/+) male mice as control group were used.
After azoxymetane (AOM)/dextran sodium sulfate (DSS) treatment GHRHKO-/- mice displayed higher Disease Activity Index (DAI) score, and more marked weight loss compared to +/+ animals. Additionally, -/- mice showed a significant increase in total colonic tumors, in particular of large size and predominantly localized in distal colon. In colonic tissue of AOM/DSS-treated -/- mice we found the presence of invasive adenocarcinomas, dysplasia and colitis with mucosal ulceration. Conversely, AOM/DSS-treated +/+ mice showed only presence of adenomas, without invasion of sub-mucosa. Treatment with AOM/DSS significantly increased prostaglandin (PG)E2 and 8-iso-PGF2α levels along with cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF)-α, nuclear factor kappa B (NFkB) and inducible nitric oxide synthase (iNOS) gene expression, in colon specimens of both groups. However, the degree of increase of all these parameters was more marked in -/- than +/+ mice.
In conclusion, generalized GHRH ablation increases inflammatory response and colon carcinogenesis in male mice. Whether this results from lack of GH or GHRH remains to be established.
OR06-04 Tissue-Specific Tumorigenesis in Multiple Endocrine Neoplasia Type I
Authors: Gardiner Juliet C 
Published: May 2020

Abstract
While a germline heterozygous mutation in the Multiple Endocrine Neoplasia type 1 (MEN1) gene predisposes tumor formation in specific tissues such as the endocrine pancreas, parathyroid glands and anterior pituitary, this tissue-specific tumorigenesis is not dependent on MEN1 mutations alone. In fact, a homozygous deletion of Men1 in mouse pancreatic exocrine tissue does not result in tumor formation, suggesting a tissue-specific mechanism. Loss of menin activates a menin-interacting protein retinoblastoma-binding-protein 5 (RBBP5). Since RBBP5 transcriptionally regulates DNA methyltransferase 1 (DNMT1), this causes global DNA hypermethylation and subsequent tumorigenesis in MEN1-target endocrine tissues. We hypothesize that while RBBP5 is ubiquitously expressed, it exclusively binds to the DNMT1 promoter in MEN1-target-tissues through its recruitment by tissue-specific factors. Using chromatin immunoprecipitation, we demonstrated that Rbbp5 is bound to the Dnmt1 promoter in MEN1-target-tissues, while not in non-target tissues. Following a high-throughput genome-wide approach, we identified two candidate factors that may recruit Rbbp5 to the Dnmt1 promoter. Immunohistochemistry showed MEN1-target-tissue-specific expression of these target factors. Co-immunoprecipitation revealed MEN1-target-tissue-specific binding of Rbbp5 to the factors. In conclusion, Rbbp5 binds the Dnmt1 promoter in MEN1-target-tissues and we have identified candidates for Rbbp5 recruitment to the Dnmt1 promoter that must be tested further to determine their role in the observed tissue specificity of MEN1-related tumorigenesis.
SUN-349 Characterizing Functional Performance in Adults with Hypophosphatasia
Authors: Dahir Kathryn , Durrough Christina , Hudson Margaret , de Riesthal Michael , Hu Jiun-Ruey , Simmons Jill 
Published: May 2020

Abstract
Introduction:
Limited data exist regarding physical and cognitive functioning of adults with hypophosphatasia (HPP), and there are no guidelines for evaluation by physical therapists (PT), occupational therapists (OT), or speech-language pathologists (SLP). We evaluated physical and cognitive functioning among adults with HPP through comprehensive assessments and patient reported outcome tools.
Methods:
Sixteen participants with HPP (median age 42 (32.5–50.5) yrs, 73% female, 100% Caucasian, 50% on enzyme replacement therapy) completed standardized assessments of mobility, balance, fine motor control, activities of daily living and cognition, as well as self-reported measures of health-related quality of life, fatigue, depression and anxiety.
Results:
Compared with normative data from community dwelling adults, participants traveled less distance on a Six-Minute Walk Test (1,376 ± 431** ft vs 1873±299) and had slower gait on a 10-Meter Walk Test (1.04±0.21 vs 1.39–1.46 m/s). Participants were slower to respond on the Nine Hole Peg Test (20.6±2.4s** for right & 21.7±2.4s** for left hand vs 16.5s to18.5s), and 2 had an abnormally slow reaction time via Dynavision (0.9s* [0.85,0.96], functional speed is &lt;1.15s). 20% scored in the low average/borderline range of performance on the Repeatable Battery for the Assessment of Neuropsychological Status, suggesting potential cognitive impairment. On the Short Form-36, 75% reported limitations in their ability to fulfill life roles due to physical problems (25%±39%ile**), 75% reported below average energy (30%±23ile**), and 100% rated their health as unlikely to improve (32%±15%ile**). Fatigue Severity Scale scores were well above the median for a healthy population (47 [34,60.5]* vs 2.3). Median scores for Depression, Anxiety, and Stress were within the normal range, but moderately severe depression was reported by 4 participants. Participants reported moderate (4), severe (1), or extremely severe (1) anxiety; and 4 reported severe (2) or extremely severe (2) stress.
Conclusions:
Objective functional assessments indicate mild deficits, but participants self-reported significant limitations due to physical dysfunction, indicating that current objective testing may not be sufficient in the HPP population. Impaired reaction time may indicate potential safety concerns with driving or certain occupations, and screening may be indicated. A subgroup of participants was significantly affected by depression, stress, and/ or anxiety. Guidelines and additional assessment tools should be created to further evaluate physical and cognitive functioning among adults with HPP. The use of PT, OT, and SLP specialists can aid in establishing baseline assessment of impairment and developing treatment plans with objective metrics for assessing efficacy of treatment.
*median
**mean
SAT-256 The Ever Confusing Cushing’s Work Up: Is It Real? Is It Pseudo Cushing’s’? Or Could It Be Factitious
Authors: Ghalib Luma , Prevedello Daniel , Mohyeldin Ahmed 
Published: May 2020

Abstract
Case Presentation:
A 50 year old female initially presented with progressive weight gain and mood swings. She had normal 24 h urine cortisol, but an elevated midnight serum cortisol. She underwent transphenoidal surgery for a presumed ACTH-dependent Cushing’s disease. Pathology was not supportive of a pituitary adenoma, showing adenohypophyseal tissue with focal expansion of the acini. The surgery was complicated by hypothyroidism and growth hormone deficiency. She was able to weaned off of the steroids after a few months. She had recurrence of her initial symptoms, she was found to have elevated late evening and morning cortisol levels. She underwent a bilateral adrenelactomy for “recurrence of the cyclical Cushing’s symptoms.” She was started on HC replacement; 10 mg AM and 2.5 mg PM, florinef 0.05 mg daily. She slowly lowered the hydrocortisone dose, and as a result lost 120 lbs.
Three years later she presented with fatigued and gaining weight, by that time she was on Hydrocortisone 3.75 mg AM, 1.25 mg evening, and fludrocortisone 0.1 mg/day. ACTH was 355 (6–48 pg/ml), serum cortisol 10 (8–19 ug/dl) on Hydrocortisone and &lt; 1.0 ug/dl off cortisone. The 24 h urine free cortisol &lt; 1.0 (10–24 ug/34h), and 17 OH- corticosteroids &lt; 4.8(4–14 mg/dl). A possible adrenal remnant was seen on abdominal CT, surgically removed of the lesion showed a lipoma.
She was referred to Neurosurgery for a second pituitary surgery for the concern Cushing’s recurrence. A pituitary MRI revealed a small potential microadenoma. The small dose of hydrocortisone was held for 48 h and an 8 AM test dose: Serum cortisol &lt; 1.20 mcg/dl (3–18), ACTH 1,077 pg/ml (5–72), 24 h urine cortisol &lt; 1.5 mcg/24h (3.5–45), 24 h urine cortisone 10 mcg/24h (17–129), and two midnight salivary cortisol were 128 and 265 ng/dl (&lt; 100 ng/dl). There was a concern raised by the laboratory for a contaminated salivary sample, as the salivary cortisol to cortisone ratio was concerning for contamination with exogenous steroid (1)
Discussion:
Work up for Cushing’s syndrome can be very confusing and frustrating at times for the patient and their physicians. Doing a meticulous work up is necessary to reach an accurate conclusion. Misdiagnosing Cushing’s can lead to a cascade of mistreatment with serious consequences. The case presented highlights the challenges encountered in taking care of such patients. It is necessary to understand the pre-testing probability to reach a precise conclusion. Factitious disorder or sample contamination can be yet another challenge in the differential diagnosis of Cushing’s work up.
(1)
Raff H Measurement of Late-Night, Salivary Cortisol and Cortisone by LC-MS/MS to Assess Preanalytical Sample Contamination with Topical Hydrocortisone. Clinical Chemistry 58:5 (2012)