bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-LB44 Cushing’s Syndrome and Illegal Receptors
Authors: Poku Caroline , Eldin Randa Sharag , Mohamed Abubakr Hassab Elrasoul Babiker , Sobia Sadiq 
Published: May 2020

Abstract
Case presentation: A 48-year-old female with HTN presented to the endocrinology clinic for the evaluation of incidental bilateral adrenal masses noted on chest CT for dyspnea workup. At the time of the presentation, she reported generalized fatigue, significant weight gain in the past year and shortness of breath. Her physical exam was remarkable for central obesity. Lab work showed elevated cortisol after 1 mg dexamethasone suppression test x 2 and elevated 24- hour urine cortisol. Plasma free metanephrine levels and aldosterone/ renin ratio were normal. MRI abdomen was done and showed bilateral adrenal masses (left: 5.6 cm, right: 3.2 cm). Patient was diagnosed with Cushing’s syndrome secondary to primary bilateral adrenal hyperplasia and was referred to endocrine surgery who recommended unilateral adrenalectomy. The decision was made to remove the larger left side adrenal mass. On post-operative day one her am cortisol decreased to 2.1 and she was started on hydrocortisone 20 mg in the morning and 10 mg in the evening.
Discussion: Primary bilateral adrenal hyperplasia is a rare cause (&lt; 2 %) of endogenous Cushing’s syndrome, usually occurs in a bimodal age distribution, in childhood and in the fifth- sixth decades. Presentation is variable with most patients having no symptoms or subclinical Cushing’s. The theory is the larger nodule size corelates with the higher cortisol production. Studies have shown between 60-70% of cases has aberrant ectopic hormone receptors which leads to increased cortisol production not only from ACTH but also from other ligands such as serotonin and vasopressin. Aberrant receptor testing examines whether cortisol or other steroid production increases in response to either physiologic or pharmacologic stimulus. Multiple genetic mutations have been associated, the most frequent is mutations in the Armadillo repeat- containing 5 gene identified in 2013. Treatment can either be medical or surgical. Medical therapy can be initiated if testing for an aberrant receptor is positive. In recent years there has been a trend towards doing unilateral adrenalectomy instead of bilateral, with initial remission of symptoms reported in about 84% of cases after unilateral adrenalectomy although there is a small risk of recurrence. Post operatively after unilateral adrenalectomy patients should be monitored for adrenal insufficiency. Our patient declined aberrant receptor testing and opted for surgery and is doing well post operatively.
Conclusion: Primary bilateral adrenal hyperplasia is a rare cause of endogenous Cushing’s syndrome which can be treated either medically or surgically.
SAT-LB72 Design of the PaTH Forward Phase 2 Trial of TransCon PTH, a Long-Acting PTH, in Patients With Hypoparathyroidism
Authors: Khan Aliya Aziz , Rejnmark Lars , Schwarz Peter E , Vokes Tamara J , Clarke Bart Lyman , Rubin Mishaela Ruth , Hofbauer Lorenz C , Erikson Erik , Palermo Andrea , Pagotto Uberto , Marcocci Claudio , Ahmed Intekhab , Mourya Sanchita , Markova Denka , Karpf David B 
Published: May 2020

Abstract
Background:
Hypoparathyroidism (HP) is caused by a deficiency in parathyroid hormone (PTH), which leads to hypocalcemia and hyperphosphatemia. Standard of care (SoC), i.e. large doses of calcium (Ca) and active vitamin D, worsens hypercalciuria and increases the serum Ca (sCa) x serum phosphate (sP) product. Studies have shown that continuous subcutaneous infusion of PTH(1-34) normalizes sCa, sP, serum magnesium, urine Ca (uCa) and bone turnover better than SoC or once- or twice-daily injections of PTH in HP patients. TransCon PTH, an investigational long-acting prodrug of PTH (1-34) transiently bound to an inert carrier via a linker, is under development as a potential once-daily replacement therapy for HP. Under physiological conditions, linker auto-cleavage occurs, releasing active PTH at a controlled rate with ~60 hour half-life. Phase 1 trial results demonstrated that once-daily TransCon PTH provided a flat, infusion like profile within the normal range of PTH 24 hours per day, increasing sCa while controlling uCa and decreasing sP, with no evidence of bone anabolic activity.
Phase 2 Design:
PaTH Forward is a global phase 2 trial evaluating the safety, tolerability, and efficacy of TransCon PTH in adult subjects with HP. Patients with HP treated with SoC were randomized at sites worldwide to daily TransCon PTH 15, 18 or 21 µg PTH(1-34) or daily blinded placebo via pen-injector for 4 weeks. The primary composite endpoint requires 1) normal albumin-adjusted sCa, and 2) normal Fractional Excretion of Ca (or ≥50% decrease from baseline), and 3) not taking active D, and 4) taking ≤1000 mg/d of Ca. After four weeks, all subjects enter an open-label extension period with the opportunity to receive TransCon PTH individually optimized to doses of 6 to 30 µg daily to evaluate long-term safety and efficacy. Other endpoints include the impact of treatment on patient experience, CaxP product, bone turnover markers, and bone mass by DXA and TBS to confirm the lack of anabolic effect.
Preliminary Results:
Approximately 55 subjects are expected to be randomized and dosed. Preliminary diary data on the initial 8 subjects completing 4 weeks of follow-up in the extension trial shows that all have discontinued SoC. Additional information will be presented at ENDO 2020. The Phase 2 trial is designed to inform the starting dose for a global pivotal phase 3 trial and evaluate TransCon PTH as a “true” PTH replacement therapy.
MON-LB106 The Effect of the Ketogenic Diet on Aldosterone Over 6 Weeks
Authors: Belany Paul A , Zhao Songzhu , Kluwe Bjoern , Kackley Madison , Buga Alex , Kline David , Brock Guy , Volek Jeff , Joseph Joshua 
Published: May 2020

Abstract
Introduction: A ketogenic diet improves type 2 diabetes, metabolic syndrome, and cardiovascular disease. Weight loss studies using caloric reduction have demonstrated a decrease in aldosterone, but there is limited data on the effect of a ketogenic diet on aldosterone. Thus, we evaluated the impact of a ketogenic diet on aldosterone in overweight or obese individuals over 6 weeks. Methods: This 3-arm prospective controlled feeding study evaluated aldosterone and renin concentrations over 6 weeks on a hypocaloric (25% energy restricted) ketogenic diet + placebo (KD+PL), ketogenic diet + ketone salt supplement (KD+KS), and a low-fat diet (LFD). Sodium intake consisted of 6100 mg, 2300 mg, and 2000 mg for the KD+KS, KD+PL, and LFD groups, respectively. Both ketogenic diets provided 40 grams(g) day of carbohydrates, 1.5 g/kg reference weight of protein and remaining calories provided as fat. The LFD provided 25% total fat, 1.5 g/kg reference weight of protein, and 100g of carbohydrates. Serum aldosterone was drawn fasting in upright position at 0, 2, 4, and 6 weeks. Scatter plots were used to explore the residual and predicted associations between aldosterone with other measures after accounting for time and group effect.Results: Twenty-four participants in the ketogenic diet groups were matched for age and body mass index, then randomized to either the KD+PL or KD+KS group. A separate group of 12 matched participants were specifically recruited for the LFD group. The median age was 33 years. Weight decreased 6, 8, and 7 kg on average in the KD+KS, KD+PL, and LFD groups, respectively, over 6 weeks (p&lt;0.05 for all). Systolic blood pressure (SBP) improved from 117 and 115 mmHg in the KD+KS and KD+PL groups to 110 mmHg over 6 weeks while the baseline mean SBP 118 in the LF group did not change. Baseline mean aldosterone of 13.6 and 13.6 ng/dL in the KD+KS and KD+PL groups increased to 33.3 and 27.3 ng/dL over 6 weeks (p&lt;0.001). Baseline mean aldosterone of 8 ng/dL in the LF group non-significantly changed to 11.5 ng/dL over 6 weeks (p&gt;0.05). Using predicted value associations, increases in ketones were positively associated with higher aldosterone (R2=0.86; p&lt;0.001). Conclusion: Participants on a ketogenic diet had significantly elevated aldosterone levels throughout the study while participants on low fat diet had little change. Unexpectedly, aldosterone was significantly higher in the high sodium vs. low sodium ketogenic diet. There was a significant association between ketones and aldosterone suggesting that ketones may play a stimulatory role on aldosterone synthesis or secretion.
MON-LB70 The Association of Paget’s Disease With Inclusion Body Myositis and Fronto Temporal Dementia (IBMFTD)
Authors: Miller Clare , Mcquaid Siobhan E 
Published: May 2020

Abstract
Background: Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is a rare, autosomal dominant condition, characterized by adult-onset muscle weakness, early-onset PDB, and premature frontotemporal dementia. Paget’s disease is a chronic disorder of bone resulting in increased bone resorption, followed by a disorganized and excessive formation of bone.
Clinical Case: A 43 year old gentleman was referred to neurology services with foot drop, limb weakness and cognitive impairment. Following a prolonged period of diagnostic evaluation a mutation in valosin-containing protein (VCP) gene was uncovered IBMPFD has a variable phenotype which may include PDB. This gentleman denied bony pain and had an alkaline phosphatase within reference range. Plain film radiographs at multiple sights demonstrated no signs of PDB. An MRI whole body was performed which reported coarse trabecular markings in L2 vertebral body and multilevel degenerative changes with bridging osteophytes in the lumbar spine consistent with PDB.
At initial review in endocrine clinic, he denied fractures or bone pain. He had no signs of increased cardiac output or cranial nerve deficits. A radionuclide bone scan identified intense radiopharmaceutical accumulation in L2 vertebral body consistent with MRI findings and also curvilinear increased activity in the left occipital bone and low-grade activity in the left hip, thus confirming polyostotic Paget’s disease.
He received a 5mg IV infusion of zolendronate, side effects of which included myalgia, pyrexia and lethargy.
Six months following the zoledronate infusion a repeat bone scan demonstrated that the extent of uptake at affected sites had decreased significantly.
He subsequently fractured his left femur following a mechanical fall. PDB can affect up to 50% of patients with IBMFTD. PDB can lead to complications such as bone pain, localized pain and deformity of the long bones, pathologic fractures and deafness. This case highlights the association of Paget’s disease with IBMFTD and as it can be asymptomatic, as in our case, radiological imaging is required for diagnosis. It also reminds us that Paget’s disease can be due to genetic causes. Understanding the role of VCP in the cell cycle may help in further understanding bone physiology.
MON-LB45 Posterior Hypothalamic Involvement on Pre-Operative Magnetic Resonance Imaging as a Predictor for Hypothalamic Obesity in Craniopharyngiomas
Authors: Rachmasari Kharisa N , Strauss Sara B , Phillips C Douglas , Lantos Joshua , An Anjile , Schwartz Theodore H , Dobri Georgiana A 
Published: May 2020

Abstract
Craniopharyngioma (CP) is a rare embryonic tumor of the sellar and parasellar region with benign histology (World Health Organization grade I) thought to arise from embryonic remnants of Rathke’s pouch. Despite its high survival rates, this tumor can lead to severe morbidity secondary to destruction of adjacent structures. Hypothalamus (HT) is a brain region that has a central role in regulating body weight through a complex mechanism involving central and peripheral signaling pathways. Destruction of its distinctive nuclei induces hyperphagia, hyperinsulinemia and weight gain. Seventy-five patients with CP who underwent first surgical resection in a single center by the same neurosurgeon between February 2005 and March 2019 were screened; those who have had prior radiation, were aged below 18 years, or did not have follow up body mass index (BMI) after surgery were excluded. Ultimately, this study included 45 patients with a mean age 50.5 years, 73.3% women. Pre and post-operative MRI were independently reviewed by three neuroradiologists to determine involvement of the hypothalamic regions: anterior, anterior and posterior, or no hypothalamic involvement. Body mass index were recorded pre operatively and subsequently after TSS up to 24 months post operation. Association between hypothalamic region involvement and BMI as well as endocrine function were examined. Posterior hypothalamic involvement seen in pre operative MRI (N=28) was significantly associated with higher BMI at 3-6 month, 7-12 month, and 13-24 month follow up (p &lt; 0.05) in comparison to involvement of anterior hypothalamic alone or no hypothalamic involvement. Similarly, posterior hypothalamic involvement in the pre and post-operative MRI was significantly associated with development of diabetes insipidus (DI) (p &lt; 0.05) compared to anterior or no hypothalamic involvement. There was no association between pre-operative BMI and hypothalamic involvement. Although the weight gain was accelerated after surgery, there was no association between post operative MRI and ensuing BMI, suggesting that the damage of the hypothalamic nuclei was done by the CP rather than surgical procedure. Conclusion: Assessment of hypothalamic involvement by anterior and posterior regions on pre operative MRI can be helpful in predicting development of obesity in patients with CP.
MON-LB128 Phosphoinositide 3-Kinase (PI3K) Inhibitor Induced Hyperglycemia With Alpelisib
Authors: Barsukova Yuliya , Jouneghani Nasrin Saleh , Islam Julie Rizwana , White Wendy 
Published: May 2020

Abstract
Intorduction: Breast cancer is estimated to be the third leading cause of cancer-related death in women. A commonly mutated pathway in breast cancer is the phosphoinositide-3-kinase (PI3K) pathway. Newer agents inhibiting PI3K are now available for the treatment of advanced cancers. Metabolic complications of new onset diabetes/hyperglycemia and hyperlipidemia are commonly seen. The precise mechanism through which PI3K inhibitors cause hyperglycemia is unknown. We present a patient who developed hyperglycemia within 2 weeks of starting alpelisib. Clinical Case: A 68 y.o female with history of metastatic invasive lobular carcinoma of the right breast HR-positive, HER-2 negative who presents for evaluation of hyperglycemia. She was diagnosed with metastatic breast carcinoma and failed multiple treatment options. She was started on alpelisib 2 weeks prior and had no history of glucose intolerance. Her pretreatment HbA1c was 5.5% (n &lt;5.7%). After initiation of alpelisib, fasting blood glucose ranged between 100-140 mg/dL (n 100-125 mg/dL), while post-prandial blood glucose ranged between 150-300 mg/dL (n &lt;140 mg/dl). Her HbA1c rose to 7% (n &lt;5.7%). She did not manifest any macrovascular or microvascular complications, but did have a family history of type 2 diabetes mellitus. After initially being started on metformin, the dose increased to 1500 mg daily with the addition of glimepiride 1 mg. She eventually achieved stable euglycemia on metformin alone.
Conclusion: Hyperglycemia has been reported to commonly occur with PI3K inhibitor therapy, the mechanism of which is poorly understood. One purposed mechanism is the effect on AMP kinase pathway which may also affect the efficacy of metformin. Here, we present a case of new onset T2DM in the setting of HR-positive, HER-2 negative breast cancer effectively treated with metformin. Future studies are needed to establish the prevalence and incidence of drug-induced hyperglycemia in patients administered PI3K inhibitors, as well as the best management approach to ensuing hyperglycemia. Reference: André F, Ciruelos EM, Rubovszky G, et.al. Alpelisib for PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer. N Engl J Med. 2019 May 16;380(20):1929-1940.
Guena, E, Roda, D, Rafii, S. Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on phase I clinical trials. Br J Cancer. 2015;113:1541-1547
Busaidy, NL, Farooki, A, Dowlati, A. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol. 2012;30:2919-2928.
SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma
Authors: Pasha Pouneh , Meneilly Graydon S , Kapeluto Jordanna Esther 
Published: May 2020

Abstract
Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N&lt95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.1, 2 Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD3. Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention4,5. This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters. References: 1) Goode PN. (1986). World J Surg 10: 586. 2) Komatsu Y. (2016) Endocr J. 63(3): 311. 3) Tarçin O. (2018). Endocrine Abstracts56 EP4. 4) Pearson RM. (1977) Clinical Pharmacokinetics vol 2: 198. 5) Allen WR. (1983). Pharmacology 27: 336.
MON-LB63 Hypocalcemia-A Clue to Digeorge Syndrome; A Very Rare Case Diagnosed in a 41 Year Male
Authors: Tharu Biswaraj , Bishal Khanal , Basnet Sijan , Adhikari Nawaraj , Tharu Sunraj 
Published: May 2020

Abstract
41-year-old male with history of anxiety, bipolar disorder, depression, cognitive developmental delay, Idiopathic Thrombocytopenic Purpura (ITP), Vit D deficiency, tinnitus, suicidal attempt, auditory hallucination, borderline intellectual functioning comes to the PCP’s office for regular follow-up. The PCP has noted that the patient was hypocalcemic on multiple visits. On exam, vitals were in normal range, height 5 feet 2 inches, BMI 31 kg/m2.Despite the patient being on calcium and Vit D2 pills for a couple of months, his Calcium level were low ranging from 5.8–7.8mg/dl (normal 8.5-10.1) with normal albumin; ionized calcium was low 0.9-0.97mmol/l (normal 1.12-1.23); Magnesium was normal 2mEq/L (normal 1.5-2.5), phosphorus slightly high 5 mg/dL (normal 2.5-4.9), PTH (ParaThyroid Hormone level) was low-normal 18.8pg/ml (normal 11.1-79.5), vitamin D 25 OH low 16ng/ml (normal 30-100); 1,25 di OH vitamin D low 8ng/ml (normal25-40).Thyroid ultrasound showed 2 benign nodules, no further work-up done. TSH and free T4 were normal. FISH (Fluorescence In Situ Hybridization) came positive for DiGeorge syndrome (deletion at 22q11.2). He was treated with calcium 600 mg 4 pills daily, calcitriol 0.25 mcg two pills daily, Vit D2 50000 IU weekly and thiazide diuretic. His labs improved.
DISCUSSIONHypocalcemia can be due to low magnesium level, drugs or associated with high or low PTH. The patient had normal magnesium and he was not on any medication that causes hypocalcemia. This rules out first two casues. Hypocalcemia with high PTH (pseudohypoparathyroidism or low vit D levels) doesn’t fall in our differential because our patient had low PTH. For hypocalcemia with low PTH, differentials include post-surgical condition (no surgical history), autoimmune (history and labs not suggestive of), infiltrative diseases (eg hemochromatosis- he had normal iron study, Wilson disease- normal copper level, granulomas- contrary he had low 1,25 Di OH vit D). Hypocalcemia secondary to genetic parthyroid gland anomaly was thought to be most likely in our patient. So FISH was pursued.
Conclusion: For patients with cognitive issues, persistence of chronic hypocalcemia (with low PTH) despite treatment should prompt for genetic disorders like DiGeorge. DiGeorge is usually the diagnosis of children. Perhaps this is the first case of DiGeorge diagnosed so late at age of 41.