bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-366 Neonatal Severe Hyperparathyroidism: Extreme Hypercalcemia as a Robust Marker for Homozygous Dosage of Pathogenic CASR Variants
Authors: Marx Stephen J , Sinaii Ninet 
Published: May 2020

Abstract
Context: Neonatal severe hyperparathyroidism (NSHPT) is a rare and life-threatening emergency. It includes generalized hyperparathyroid bone disease and respiratory distress from combinations among a narrowed thorax, rib fractures, hypotonia, and biochemical disturbances. Successful therapy is compatible with long life and a healthy prognosis. However, neuromotor retardation may persist after otherwise successful therapy. The time and amplitude of hypercalcemia likely correlate with irreversible neuromotor retardation; thus, early intervention seems critical in many cases. NSHPT is usually caused by homozygous or heterozygous pathogenic variant(s) of the CASR; a heterozygous variant of this gene is also the usual cause of familial hypocalciuric hypercalcemia (FHH or FHH1). Homozygotes and heterozygotes with NSHPT are often not distinguished in the current literature. In theory, their management should differ. Optimum treatment in homozygotes is early total parathyroidectomy with induction of postoperative hypoparathyroidism. Optimal management of heterozygotes is more complex. It consists in temporizing measures and varies from careful observation without surgery, to bisphosphonates and/or calcimimetics, and to subtotal parathyroidectomy. The heterozygotes can then develop into healthy babies with asymptomatic FHH1.
Evidence Acquisition: Each case met strict criteria for “severe” and neonatal disease. We analyzed the core biochemical parameters of the maximal serum calcium and maximal PTH. To compare different immunoassays, PTH was analyzed as a ratio (thus without units) of the raw data divided by the upper limit of its normal range. Each case also required information about the allelic dosage of the pathogenic or likely pathogenic CASR variant(s).
Evidence Synthesis: There were 36 cases with homozygous pathogenic CASR variants and 21 cases with heterozygous pathogenic or likely pathogenic variants. Maximal serum calcium was far higher in homozygotes 5.8 +/- 1.5 versus 3.2 +/- 0.2 (P&lt;.001) (normal 2.2–2.6 mM). Maximal serum PTH as a ratio was also far higher in homozygotes 17 +/- 12 versus 8 +/- 9 (P=.003) (normal ratio 0.3–1.0). We defined extreme hypercalcemia empirically as any calcium value above 4.5 mM. No heterozygote had a maximal calcium above 3.7 mM; however, 30 of 36 (81%) of the homozygotes had maximal calcium above 4.5 mM. Whenever tested early, this extreme hypercalcemia was usually recognized in the first week of life.
Conclusions: Extreme hypercalcemia greater than 4.5 mM was newly identified as a conservative cutoff that was 100% predictive of homozygosity for pathogenic CASR variants. Extreme hypercalcemia in NSHPT is an early, facile, rapid, and inexpensive determinant of homozygosity for pathogenic variants of the CASR. It should be sought and used to promote early and definitive total parathyroidectomy, whenever it is identified in NSHPT.
SAT-508 Oh My Thyrotoxic Heart! An Uncommon Presentation of High Output Heart Failure
Authors: Morales Maria Del Mar Felix , Nieves Rebeca Vazquez , Olan Jonathan Torrens , Maymi Lorianna Aleman , Bracero Xiomara Cruz , Carrero Quiñones Milton D 
Published: May 2020

Abstract
High output heart failure is an extremely rare manifestation of thyrotoxicosis in patients without heart disease. Thyroid hormone has a potent metabolic, vascular, positive chronotropic and inotropic effects. Thyrotoxicosis is accompanied by a reduction in systemic vascular resistance and an obligatory increase in cardiac output to compensate high metabolic state. Most of the patients had completed or near completed recovery of cardiac function after treatment to euthyroid status, if cut in time.
Case of 70 y/o female with past medical history of hypothyroidism, hypertension and chronic smoker, came to emergency room due to lightheadedness, weakness, shortness of breath, palpitations and acute bedridden for one week ago. Denied fever, nausea, vomiting or chest pain. On examination patient presented with 122bpm, 23rpm and normotensive. She was in acute respiratory distress requiring BiPAP. Lungs auscultation bilateral crackles, decrease sounds in the bases. Cardiac exam significant for tachycardia, lower extremity edema and JVD +. Laboratories significant for CKD stage 2, chronic anemia and hypoxemia. EKG no ST changes neither T depressions. CXR day #1 reported no cardiopulmonary disease. Basing in these she was admitted with Suspected Pulmonary Embolism. Well’s score was moderate risk; a Chest CTA and full anticoagulation were ordered. Later, venous duplex reported no DVT and D-dimer levels 1.65μg/ml. TSH levels significant decrease 0.0002mU/L and T4 1.800ng/dL. CXR Day#2 reported pulmonary edema and pleural effusion. ECHO2D moderate LVH and preserved systolic function. Patient referred her doctor recently increased thyroid medications from 50 to 100 mcg. Instead of presenting with pulmonary embolism, she has hyperthyroidal state causing cardiac failure. Levothyroxine, heparin and Chest CTA scan were cancelled. She was started in Atenolol and diuretics. Patient symptoms improved and was discharged home to be followed in the clinic. After one week, TSH levels were in 0.008mU/L and one month later in 3.032mU/L. She was started in Levothyroxine 50mcg, to maintain patient euthyroid state.
This case illustrates that sometimes tachycardia and tachypnea are symptoms which frequently presents as baffling diagnostic problems. The association of thyrotoxicosis and cardiovascular morbidity is well established. Thyrotoxicosis most common cardiac manifestation is high output heart failure. Patients presenting with heart failure may have thyrotoxicosis as the underlying cause. Treatment of the thyrotoxicosis can restore normal heart function. Hyperthyroidal state may be take into consideration as a differential of tachycardia and tachypnea even if it’s not one of the common causes. Awareness of this presentation may help identify patients with reversible dilated cardiomyopathy and other complications.
MON-272 Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients
Authors: Yamamoto Koichiro , Hanayama Yoshihisa , Hasegawa Kou , Yasuda Miho , Tokumasu Kazuki , Hagiya Hideharu , Ogawa Hiroko , Obika Mikako , Otsuka Fumio 
Published: May 2020

Abstract
PRL is a polypeptide hormone that is, in phylogeny, well conserved but elicits various species-dependent functions. PRL is related to the regulation of osmotic pressure in fish and amphibians, fat retention in reptiles and birds, and glucose-lipid metabolism, bone homeostasis and development of the mammary gland in mammals. In humans, PRL secretion is regulated in an inhibitory manner by dopaminergic neurons that project from the hypothalamus to PRL-producing cells in the anterior pituitary gland. Since dopaminergic actions are mainly mediated by D2R, various agents that bind D2R can affect serum PRL levels. In the clinical aspect, hyperprolactinemia is considered in cases with galactorrhea, infertility and sexual dysfunction. Other causes of hyperprolactinemia include hypothyroidism, chronic kidney disease and pregnancy. Also, PRL receptors have been considered as therapeutic targets for some cancers and autoimmune diseases. Given that several pathophysiological functions related to PRL have been recently uncovered, the utility of measuring serum PRL levels could be more widely applicable for a clinical setting. We therefore attempted to reveal the relevance of PRL levels to various clinical parameters in patients who visited a general medicine department. We reviewed medical records of 353 patients whose serum PRL levels were measured in our department during the period from 2016 to 2018. Patients lacking detailed clinical records (n=194) and patients taking medications that affect D2R (n=19) were excluded from this study. Data were analyzed for 140 patients (42 males, aged 49 ± 18 years; 98 females, 45 ± 19 years) in whom various pain and general fatigue were major symptoms at the first visit and in whom hypertension and dyslipidemia were frequently seen in past histories. Average PRL levels were significantly lower in males than in females. The median PRL level in males was 6.5 ng/ml (IQR: 4.2–10.3) ng/ml and that in females was 8.1 ng/ml (5.9–12.9). Patients were divided into two groups depending on whether PRL levels were higher than 10 ng/ml. The group of males with relatively high PRL levels (≥10 ng/ml) had significantly lower levels of serum albumin and higher levels of serum LDH. Of note, there were significant correlations of male PRL levels to erythrocyte sedimentation rate (ESR) (r=0.6), serum LDH (r=0.4) and albumin level (r=-0.5), and TSH/FT4 ratio (r=0.5). On the other hand, female PRL levels were negatively correlated to age (r=-0.2) and serum levels of FSH (r=-0.3) and positively correlated to serum levels of GH (r=0.3). Collectively, the results revealed that PRL levels had gender-specific relevance to various clinical factors. It is notable that PRL levels in males were related to inflammatory status shown by high ESR and low serum albumin and were also associated with a hypothyroid condition.
MON-668 The Content of Serum Clusterin in Patients with Diabetic Macular Edema Depending on the Kind of Glucose Lowering Therapy
Authors: Kyryliuk Mykhailo L , Suk Sviatoslav A 
Published: May 2020

Abstract
Relevance. Insight into the pathophysiology of diabetic macular edema (DME) has led to novel treatments, including anti-VEGF, corticosteroid-based treatment strategies and novel therapies, such as a clusterin blood retina barrier (BRB) cytoprotection. It has been shown the protective effect of clusterin on oxidative stress-induced cell death and its emerging roles in reduction of both BRB breakdown and neural retina damage. Goal. To assess the content of serum clusterin in patients with type 2 diabetes (T2D) and diabetic macular edema depending on the type of glucose lowering therapy. Material and methods. This study was conducted in 82 patients with T2D and DME. The average age of patients was 65.25 ± 10.85 years (±SD) [25; 84], the average duration of diabetes was 14.0 ± 7.05 years (±SD) [1; 35], the average level of HbA1c was 8.40 ± 1.58% (±SD). The criteria for inclusion in the open study was voluntary informed consent, age 18 years and more, the presence of T2DM. Non-inclusion criteria were the presence of endocrine diseases, which can lead to type 2 diabetes, T1D, acute infectious diseases, cancer, decompensation of comorbid pathology, mental disorders, antipsychotics, antidepressants, neurodegenerative diseases of the central nervous system, proteinuria, damage to the optic nerve, glaucoma and mature cataracts. 43 patients received oral glucose lowering drugs (OGLD: sulfonylureas, biguanides), 39 patients received insulin therapy. All patients had instrumental ophthalmological examinations. The concentration of serum clusterin was measured by «Human Clusterin ELISA» kits. Statistical analysis was performed by one-way ANOVA analysis. Results. A study of level variability of blood clusterin in patients with DME showed its dependence from the type of glucose lowering therapy. Comparison of mean values of strum clusterin in patients with DME and T2DM revealed the following statistically significant differences: OGLD 87,08 ± 3,15 mcg/ml [95% CI 82,63 - 91,54 mcg/ml]; insulin therapy 74,79±2,98 mcg/ml [95% CІ 70,58 - 78,99 mcg/ml] (р=0,006). Apparently, clusterin is involved in the pathogenesis of DME and may have a potential in reducing of the pathogenic effect of diabetes on the neurovascular unit. The data obtained make it possible to discuss the neuroprotective role of clusterin in DME with the use of voiced oral hypoglycemic drugs, which usually prescribe for patients with mild form of T2D or for the patients with moderate severity T2D (i. e. at the initial stages of development of diabetes). Conclusion. Against the background of glucose lowering drugs in patients with type 2 diabetes and diabetic macular edema statistically significant (р=0,006) increases the content of serum clusterin compared to insulin therapy.
MON-378 Efficacy and Safety of Romosozumab vs Alendronate Is Similar Across Different Levels of Renal Function Among Postmenopausal Women with Osteoporosis
Authors: Miller Paul , Cheung Angela M , Reid Ian , Rojeski Maria , Vanderkelen Mark , Yang Wenjing , Santiago Norma Ruiz , Oates Mary 
Published: May 2020

Abstract
Postmenopausal women with osteoporosis may also have renal insufficiency. We conducted a post hoc analysis of the ARCH study to determine the efficacy and safety of romosozumab (Romo) vs alendronate (ALN) among patients with different levels of baseline renal function.
In ARCH, 4,093 postmenopausal women, 55–90 years old, were randomized 1:1 to receive monthly subcutaneous Romo 210 mg or weekly oral ALN 70 mg for 12 months (double-blind phase [DBP]). Eligible patients had a bone mineral density (BMD) T score of ≤ –2.5 at the total hip (TH) or femoral neck (FN) and either ≥ 1 moderate/severe vertebral fracture (VFx) or ≥ 2 mild VFx; or a T score of ≤ –2.0 at the TH or FN and either ≥ 2 moderate/severe VFx or an Fx of the proximal femur sustained 3–24 months before randomization. Pts were excluded for significantly impaired renal function (eGFR &lt; 35 mL/min/1.73 m2, calculated using the MDRD equation). For the current analysis, patients were categorized by baseline eGFR: normal renal function (eGFR ≥ 90), mild renal insufficiency (eGFR 60–89), or moderate renal insufficiency (eGFR 30–59). The least squares mean (LSM) % change from baseline in BMD at the lumbar spine (LS), TH, and FN; incidence of new VFx; incidence of adverse events (AEs); and changes in renal function were assessed for each eGFR category at month 12 of the DBP.
At baseline, 15% of patients had eGFR ≥ 90, 60% had eGFR 60–89, 24% had eGFR 30–59, and 0.3% had eGFR 15–29. In the overall patient population, LSM % change (95% CI) from baseline in BMD (Romo vs ALN) was 13.7% (13.4–14.0) vs 5.0% (4.7–5.2) for LS, 6.2% (5.9–6.4) vs 2.8% (2.7–3.0) for TH, and 4.9% (4.7–5.2) vs 1.7% (1.5–2.0) for FN (P &lt; 0.001 at each site). Changes in BMD were similar irrespective of baseline eGFR. Among patients with eGFR ≥ 90, eGFR 60–89, and eGFR 30–59, the incidence of new VFx (Romo/ALN) was 3.3%/7.3% (relative risk reduction [RRR] = 57%; 95% CI: 1–81), 3.2%/3.9% (RRR = 19%; 95% CI: -28–49), and 3.4%/6.2% (RRR = 51%; 95% CI: 5–75), respectively. The incidences of AEs, serious AEs, and fatal AEs were similar in both treatment groups within each eGFR category as well as across eGFR categories; there was a higher incidence of positively adjudicated cardiovascular events in the Romo vs ALN group overall and across eGFR categories. One patient in the Romo group with eGFR 60–89 at baseline and 1 in the ALN group with eGFR ≥ 90 at baseline had an AE of mild hypocalcemia. Similar percentages of patients in the Romo and ALN groups had changes in renal function over 12 months of treatment.
In conclusion, the efficacy and safety of Romo vs ALN was similar across different levels of renal function.
SUN-191 The Creatinine, the Crib and the Manometer - Navigating the Labyrinth of Primary Aldosteronism
Authors: Hashmi Hiba , LaFave Laura 
Published: May 2020

Abstract
A 21-year-old Ethiopian female with a five-year history of hypertension presented to medicine clinic with headaches and fatigue for two weeks. She was hypertensive to 163/113 mmHg. She had recently moved to the US and no prior medical records were available. She had been taking an unknown antihypertensive until three weeks prior. She was found to have a creatinine of 3.49 mg/dL. Renal ultrasound revealed bilateral, small echogenic kidneys without any evidence of renal artery stenosis. An intrauterine pregnancy was also incidentally discovered. Her aldosterone level was elevated to 486 ng/dL and her renin activity was 1.3 ng/ml/hr, with a ratio of 373, diagnostic of primary aldosteronism. Due to the markedly high ratio, a saline suppression test was deemed unnecessary for confirmation. Her serum potassium was normal at 3.6 mEq, likely due to poor renal clearance. Given renal failure, a CT non-contrast of the adrenal glands was performed with normal findings. She elected to terminate the high-risk pregnancy.
Based upon her young age at presentation, family history of early onset hypertension, grossly elevated aldosterone: renin ratio and unrevealing workup for a primary tumor or hyperplastic adrenals, a diagnosis of familial hyperaldosteronism was considered. She failed a month-long trial of dexamethasone therapy, therefore glucocorticoid remediable aldosteronism was excluded. She was subsequently started on spironolactone with good response. Adrenal vein sampling was considered to find a surgical target for adrenalectomy but could not be performed given worsening kidney function. After discussion with Nephrology she opted for a pre-emptive renal transplant evaluation, rather than pursuing dialysis. Genetic testing for subclassification has been negative for mutations in KCNJ5 and CACNA1H with ongoing testing for novel mutations.
Primary aldosteronism (PA) usually presents with recalcitrant hypertension, hypokalemia and an elevated aldosterone: renin ratio. It is commonly attributed to adrenal adenomas or hyperplasia with familial hyperaldosteronism (FH) remaining a rare etiology. FH is sub-divided into glucocorticoid remediable, type I, and non- glucocorticoid remediable, types II – IV. The initial diagnosis of such a condition during pregnancy and in the setting of worsening kidney disease presents a diagnostic and management challenge as this precludes adrenal vein sampling and contrast imaging. Our case highlights the importance of early screening for PA and illustrates the need for updated guidelines on aldosteronism workup in the setting of ESRD and pregnancy.
SUN-200 Adrenal Cortical Neoplasm with Progression to Metastatic Adrenal Cortical Carcinoma One Year After Adrenalectomy
Authors: Sands Mollie , Zhang Jian , Tan Marilyn , Hoffman Andrew R 
Published: May 2020

Abstract
Background: Adrenal cortical carcinoma (ACC) is a rare and aggressive malignancy; diagnostic tools for a pathologic confirmation of ACC are currently limited to scoring systems such as the modified Weiss criteria, the Helsinki score, and criteria proposed by Bisceglia et al. There is lack of consensus on appropriate monitoring and therapeutic strategies for suspicious lesions that do not fulfill all criteria for malignancy or metastatic potential. This is a case of a previously resected localized adrenal neoplasm with progression to metastatic ACC 1 year later.
Clinical Case: A 63-year-old male with hypertension and type 2 diabetes was referred to Endocrinology due to fragility fractures, weight gain, and uncontrolled hypertension concerning for cortisol excess. Workup revealed a 24-hour urinary free cortisol of 283 μg [0–50 μg/24hr], a post-1 mg dexamethasone suppression cortisol of 24.6 μg/dL [&lt;1.8 μg/dL], and a random ACTH of &lt;1.1 pg/mL. CT adrenals revealed a left 3.3 cm nodule measuring 40 Hounsefield units and 27% washout. The patient underwent left adrenalectomy with clear margins. Pathology reported an oncocytic adrenal cortical neoplasm with a Ki-67 of 4.3%, an elevated mitotic activity of up to 12 mitoses per 50 high-power fields, and large nuclei with prominent nucleoli. There was no evidence of necrosis, capsular or vascular invasion. The final pathologic diagnosis was “adrenal cortical neoplasm with worrisome features”, and close follow-up was recommended. 1 year later, the patient presented with recurrent Cushing’s syndrome; he was found to have metastatic ACC with lesions in the adrenalectomy bed, liver, and lungs. Despite maximal medical therapy, the patient suffered severe sequelae of Cushing’s and transitioned to palliative measures.
Clinical Lessons: There are several pathologic scoring systems used to diagnose and predict prognosis in ACC. The challenge of this case is balancing fulfilling the highly-sensitive Bisceglia criteria for ACC [1 “major criterion” of high mitotic rate favors oncocytic ACC] with the other aspects that suggest a more positive outcome: clear surgical margins and a Helsinki score of 7.3 [≥8.5 favors metastatic potential]. His diagnosis fell into an intermediate area of “neoplasm with worrisome features”, and he did not receive adjunctive mitotane therapy. Current guidelines do not recommend adjuvant mitotane therapy for indeterminate lesions or for cases of confirmed ACC with Ki-67 &lt;10% after complete resection, and there is limited guidance regarding monitoring of such lesions. Retrospectively, it is unclear if our patient would have had an improved outcome with adjunctive mitotane therapy or closer surveillance for recurrence.
Bisceglia M, Ludovico O, Di Mattia A, Ben-Dor D, Sandback J, Pasquinelli G, Lau SK, Weiss LM. Adrenocortical Oncocytic Tumors: Report of 10 Cases and Review of the Literature. Int J Surg Pathol. 2004 Jul; 12(3)231–43
OR31-02 Diagnostic Criteria for Polycystic Ovary Syndrome in Adolescents: Impact on Prevalence and Longitudinal Body Mass Index Trajectories
Authors: Tay Chau Thien , Teede Helena Jane , Hart Roger , Earnest Arul , Doherty Dorota , Hickey Martha , Moran Lisa J , Joham Anju Elizabeth 
Published: May 2020

Abstract
Background: Polycystic ovary syndrome (PCOS) is characterised by oligo-anovulation (OA), hyperandrogenism (HA) and polycystic ovary morphology (PCO). While the Rotterdam criteria (defined as 2 out of 3 features) are the most widely used criteria in adults, controversy remains for the diagnostic criteria in adolescents as many PCOS features overlap with normal pubertal physiological changes. The 2018 international evidence-based PCOS guideline recommends modified Rotterdam criteria (OA and HA) in adolescents based on expert consensus. We aimed to 1) compare the prevalence of PCOS using original and modified Rotterdam criteria in an unselected adolescent cohort and 2) explore the association between diagnostic phenotypes and long-term body mass index (BMI) trajectories. Methods: 227 adolescent females of the Western Australian Pregnancy Cohort (Raine) Study undertook detailed PCOS assessment at the mean age of 15.3 years (mean age of menarche 12.4 years). Detailed anthropometric measurements were collected from birth until age 22 years. T-test was used for group BMI comparisons and longitudinal BMI was analysed using Generalised Estimating Equations with PCOS by time and PCOS phenotypes by time as interaction terms. Results: PCOS was diagnosed in 66 (29.1%) participants using original Rotterdam criteria versus 37 (16.3%) participants using modified Rotterdam criteria. Using modified Rotterdam criteria, participants with PCOS had higher mean group BMI than participants without PCOS from age 5 years onwards. Significant interaction was detected between PCOS and time (p&lt;0.001) on longitudinal BMI gain where higher BMI gain was observed in participants with PCOS from age 14 years onwards. Only the modified criteria phenotype was significantly associated wth long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories as participants without PCOS (p&lt;0.001). Conclusions: Our findings validate the PCOS guideline recommendation as modified Rotterdam criteria reduce over-diagnosis of PCOS in adolescents and accurately identify the phenotype at risk of long-term weight gain. The BMI trajectories of females with and without PCOS diverge from early childhood suggesting that metabolic dysfunction in PCOS commences early in the pre-pubertal period. Disclosures: Nothing to disclose. Funding: PCOS CRE scholarship and Research Training Program Scholarship awarded to CT; NHMRC Medical Research Future fund awarded to HT; National Heart Foundation Future Leader Fellowship awarded to LM; NHMRC early career fellowship awarded to AJ.