bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-LB67 Revisit Serum Calcium Correction
Authors: Li Yulong , Zhu JunJia , Blau Jenny , Simonds William F 
Published: May 2020

Abstract
Context: The serum calcium level is one of most routinely ordered tests in clinical practice. Many factors can affect calcium level and its interpretation. There are challenges and barriers in applying calcium correction formulas to every-day practice. Objective: Revisit correlation between total and ionized calcium levels, and dependence of serum calcium on albumin, pH and creatinine levels. Methods: This study included 1537 subjects enrolled in a parathyroid disease clinical protocol. We examined calcium and relevant biochemistry tests collected simultaneously and repetitively over consecutive years. Histograms, repeated measures correlation, correlation plots, and liner regression plots were used to analyze and visualize the data. Results: We found that: 1) directly measured total serum calcium and ionized calcium had excellent correlation and dependence with p-value=2.2e-16, repeated measures correlation coefficient (rmcorr)=0.919, and 95% interval (CI) = 0.916 to 0.922; 2) there was a low dependence between total serum calcium and albumin levels (rmcorr=0.454, 95% CI=0.433 to 0.474), a low dependence between ionized calcium and pH levels (rmcorr=-0.309, 95% CI= -0.326 to -0.292), and no dependence between total calcium and creatinine levels (rmcorr=0.026 95% CI=0.012 to 0.040); 3) using the commonly applied correction formulas, to either adjust total calcium based on albumin levels or else adjust ionized calcium based on pH levels, did not improve dependence among them. Conclusions: We therefore suggest using directly measured total serum calcium and/or ionized calcium level to assess clinical calcium status in general patients tested for parathyroid related disorders.
SAT-LB48 Novel Genetic Variant of Carney Complex With Acromegaly
Authors: Cristiano Elizabeth , Miles John M , Bhattacharya Rajib 
Published: May 2020

Abstract
Objective: To describe an uncommon case of Carney complex with acromegaly secondary to pituitary microadenoma with a novel genetic variant. Background: Carney complex (CNC) is a rare autosomal dominant syndrome characterized by myxomas, pigmented skin and mucosal lesions, as well as multiple endocrine tumors. The etiology is an inactivating mutation of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A). Recently, additional CNC pathologic variants in PRKACA and PRKACB have been identified.[1] Elevated growth hormone (GH) and IGF-1 levels are sometimes seen in patients with CNC, thought to be secondary to somatotroph hyperplasia. However, less than one fifth of patients with CNC have clinical acromegaly. [2] Case: Here we describe a 35-year-old female diagnosed with atrial myxoma after presenting with fatigue in her 20s. After her fatigue failed to resolve following surgical excision, further investigation revealed an ovarian tumor. The patient sought care in Mexico where she underwent radiation for presumed ovarian malignancy. Review of the ovarian lesion biopsy at a university hospital later revealed benign melanocyte proliferation. She subsequently developed amenorrhea and hirsutism which prompted referral to endocrinology. Evaluation revealed coarse facial features, large hands, elevated IGF-1, and positive GH suppression test leading to a diagnosis of acromegaly. Gene sequencing revealed a novel pathologic variant of PRKAR1A consistent with CNC. MRI brain was originally negative for pituitary lesions; however follow up imaging after our visit with the patient showed a hypoenhancing lesion concerning for a pituitary microadenoma. Neurosurgical evaluation is underway. Discussion: Acromegaly with a pituitary adenoma is uncommon in patients with CNC. However, clinicians should have high suspicion for the disease in patients with CNC and other endocrine neoplasia disorders. The diagnosis has many deleterious consequences if not treated early. Additionally, this case represents a novel pathologic variant of PRKAR1A that has not previously been identified in Carney complex. References: 1. Correa, R., P. Salpea, and C.A. Stratakis, Carney complex: an update. Eur J Endocrinol, 2015. 173(4): p. M85-97. 2. Pack, S.D., et al., Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the “complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas” (Carney complex). J Clin Endocrinol Metab, 2000. 85(10): p. 3860-5.
SAT-LB125 Broad Spectrum Effects of a Ketogenic Diet Delivered by Remote Continuous Care on Inflammation and Immune Modulators in Type 2 Diabetes and Prediabetes
Authors: Phinney Stephen , Adams Rebecca , Athinarayanan Shaminie , McKenzie Amy , Volek Jeff 
Published: May 2020

Abstract
Type 2 diabetes (T2D) is associated with, and often preceded by, increased levels of circulating c-reactive protein (CRP) and WBC count that mediate the body’s inflammatory and immune responses (inflammatory mediators [IMs]). This relationship between inflammation and diabetes is complex, as statins have anti-inflammatory properties but paradoxically promote or exacerbate T2D. Recently it has been reported that beta-hydroxybutyrate levels characteristic of nutritional ketosis enhance cellular defenses against oxidative stress and block the assembly of the NLRP3 inflammasome. As part of an ongoing study of the effects of a well-formulated ketogenic diet (WFKD) delivered via a web-based continuous care intervention (CCI) on 262 patients with T2D1 and 116 with prediabetes (PreD), we determined plasma levels of 16 IMs at baseline, 1 yr, and 2 yrs. These same IMs were concurrently monitored in 87 patients with T2D recruited as usual care controls (UC). At baseline, a statin was prescribed for 50% of the T2D/CCI patients, 27% of PreD/CCI patients, and 59% of the T2D/UC patients; at which time statin use was associated with reduced plasma CRP (P=7 x 10-5) compared to non-statin users in the T2D/CCI group only. There were no other significant baseline differences between statin users and non-users for any IMs (WBC, TNFa, IL-1b, IL-6, IL-8, IL-18, IFN-g, E- L-, and P-selectins, EGF, VEGF-A, MCP-1, ICAM-1 and VCAM-1). After 1 yr and 2 yrs of the CCI, mean weight losses in T2D were 12% and 10%, HbA1c reductions were 1.3% and 0.9%, and diabetes medication use was reduced by 51% and 53%, respectively. Linear mixed effects models were used to assess change in IMs over the 2 yrs, facilitating intent-to-treat analyses. Fourteen of the 16 IMs (excluding ICAM-1 and VCAM-1) were reduced compared to baseline in T2D/CCI (P&lt;0.001), with none showing significant increases between yrs 1 and 2. A similar pattern albeit at lower magnitudes was seen in patients with PreD/CCI. Despite lower CRP values at baseline, T2D/CCI patients prescribed a statin experienced further reductions with the WFKD over the 2 years (P=3 x 10-5). In the T2D/UC group, no significant changes in any of the IMs were observed at 1 yr or 2 yrs. These observations suggest that a WFKD delivered via the CCI has broad-spectrum anti-inflammatory and immune modulatory effects in patients with T2D and PreD. Consistent with prior reports, statin use was associated with reduced CRP at baseline in the T2D/CCI group, but this effect was not significant in PreD/CCI and T2D/UC groups. CRP reductions were nonetheless significant in T2D/CCI statin users, suggesting added benefit of the WFKD. We conclude that improvements in IMs induced by a combination of nutritional ketosis and weight loss contribute to the beneficial effects of the CCI in the management of T2D.
1. Athinarayanan SJ, et al. Front Endocrinol. 2019. 5;10:348
MON-LB80 Human Thyroid Cancer Cells Are Highly Sensitive to CDK7 and 9 Inhibition
Authors: Rajan Neel , Bautista Luis , Adik Amy , Ringel Matthew David 
Published: May 2020

Abstract
Cancer cells display lineage and cancer-specific transcriptional control of expression of oncogenic driver genes, particularly those regulated through super-enhancers. Compounds that target CDK7 and 9, key regulators of RNA polymerase II (RNAPII)-mediated gene transcription, selectively reduce transcription of “superenhanced” oncogenes and are in clinical trials. We previously identified that medullary cancer cell lines are highly sensitive to CDK7 inhibition and that the RET-gene is super-enhanced. In the present study, we sought to determine sensitivities of a panel of follicular cell-derived thyroid cancer cell lines to the CDK7 inhibitor, THZ1 and CDK9 inhibitor, AZD4573. We selected 8 independently confirmed thyroid cancer cell lines (TPC1, FTC133, BCPAP, SW1376; K1, THJ16, C643, and 8505C) from a variety of histological subtypes with different drive mutations and performed WST assays with increasing concentration of THZ1 or AZD4573 to determine IC50 for each cell line. Western blots were performed in parallel for target validation. IC50 values ranged from 5-100 nM for both compounds for all cell lines. All cell lines showed inhibition of CDK 7 phosphorylation (Ser 5) of RNAPII with retained CDK7 levels with THZ1 and loss of CDK9 RNAPII phosphorylation (Ser 2) with both compounds. However, treatment with either agent unexpectedly caused a reduction of total RNAPII protein levels. qRT-PCR did not reveal reduced mRNA levels in TPC1 cells with THZ1 treatment while, Bortezomib (proteasome inhibitor) co-treatment with THZ1 rescued RNAPII protein. These results are consistent with THZ1-induced proteasome degradation of RNAPII. BRAF protein levels also decreased in the hemizygous BRAF V600E-mutated cell line (8505C) but not the BRAF WT cell line (TPC1). qRT-PCR of both cell lines treated THZ-1 showed stable BRAF gene expression; further mechanistic studies are ongoing. In summary, human thyroid cancer cell lines are sensitive to inhibition of CDK7 and CDK9 likely through several mechanisms not all directly attributable to RNAPII inhibition.
SUN-930 A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine Tumour
Authors: Bahrami Jasmine , Mete Ozgur , Prebtani Ally 
Published: May 2020

Abstract
A Case of Acromegaly Secondary to Ectopic Growth Hormone-Releasing Hormone (GHRH) Secretion from a Bronchial Neuroendocrine Tumour
Background
Acromegaly due to ectopic GHRH secretion is a rare disorder and only accounts for less than 1% of all cases of acromegaly.
Case
We present the case of a 42-year old female with acromegaly from a bronchial neuroendocrine tumour (NET) secreting GHRH. The patient presented with gradual onset of dyspnea and wheezing. Subsequent imaging (chest X-ray, CT chest) revealed a large left-sided thoracic mass. Bronchoscopy was performed and a biopsy was taken from the mass. Initial histological examination reported small cell lung carcinoma (SCLC). Therefore, she underwent chemoradiotherapy. The patient was concurrently experiencing increased digital girth, weight gain, and enlarged tongue and was therefore referred to our endocrinology clinic for evaluation of acromegaly. Investigations revealed normal ACTH, markedly elevated IGF-1 (1031 μg/L, normal 63–215 μg/L), and non-suppressed GH levels following a 75g oral glucose tolerance test. The remainder of the pituitary panel, including TSH, prolactin, FSH, LH were all normal. An MRI sella showed a completely normal pituitary and pineal gland with no evidence of brain metastasis. She thus met clinical and biochemical criteria for acromegaly but a pituitary source could not be identified. Given her history, a paraneoplastic process or ectopic GHRH-producing tumour was suspected. Further workup showed a significantly elevated circulating GHRH levels of 73 pg/mL (normal 5 – 18 pg/mL). Subsequently, a second pathologist with expertise in NETs reviewed the same biopsy specimen. The specimen was found to be a GHRH-producing well differentiated pulmonary NET with a Ki67 index of 1.5%, and thus not a SCLC. Furthermore, a somatostatin receptor scintigraphy study was done which showed evidence of a somatostatin avid receptor rich lesion in the lung, corresponding to the known tumour. Thus, what initially appeared to be a SCLC was subsequently found to be a GHRH-secreting NET, illustrating the challenges of diagnosing these rare tumours. She was treated with intramuscular sandostatin 20mg q28days and then underwent a left pneumonectomy, resulting in biochemical resolution of her acromegaly (IGF-1 219 μg/L). Genetic testing for MEN1 was also completed as there is an association between ectopic GHRH NETs and MEN-1; however, genetic testing revealed no pathogenic variants and exon deletions or duplications suggestive of MEN-1.
Learning points
Diagnosis of acromegaly due to ectopic GHRH secretion requires high clinical suspicion by the treating clinicians (e.g., endocrinologist, oncologist) as well as review of histology by expert pathologists. Our case highlights that ectopic GHRH secretion is a rare but important cause of acromegaly, which should always be suspected when a clear pituitary cause is not identified.
SAT-339 Calcium Level in a Patient with Rhabdomyolysis. A Tale of Two Phases
Authors: Samargandy Shaza Ahmed 
Published: May 2020

Abstract
Background: Calcium kinetics can be challenging during the different phases of rhabdomyolysis1. We herein report a case of sever hypercalcemia refractory to hemodialysis following a period of hypocalcaemia that developed in a patient with rhabdomyolysis.
Case: A 27-year-old male patient was diagnosed with meningoencephalitis complicated with septic shock, continuous seizures, rhabdomyolysis, acute kidney injury and oliguria. His creatinine was 219 μmol/L (53–115), urea was 8 mmol/L (2.5–6.4). Creatine kinase (CK) was significantly high above assay range. Corrected serum calcium was 1.82 mmol/L (2.12- 2.52), phosphate was 0.48 mmol/L (0.81–1.58). He required intermittent sessions of hemodialysis and antibiotics therapy which both have been initiated since the first day of admission. Initially he had hypocalcaemia but as rhabdomyolysis improved, his calcium levels started to rise to reach normal levels by day 13 post admission. By day 16, he started to gradually develop hypercalcemia. Initially, it was 2.73 mmol/L and in another 10 days it was 3.39 mmol/L and reached maximum of 3.90 mmo/L despite the intermittent dialysis sessions. PTH was supressed at 0.62 Pmol/L. Over that time, his renal functions and urine output were gradually improving.
The clinical impression was PTH independent hypercalcemia and the work up for that was initiated. CT chest, abdomen and pelvis did not reveal any suspicious masses, lytic bone lesions, or lymphadenopathies. His acid fast bacilli stain and culture were both negative. His chest imaging did not show any findings to suggest sarcoidosis. TSH was normal and random cortisol was 339.2 nmol/l with albumin 20g/L. HIV serology came back negative.
He received Calcitonin 500 IU BID for three days and Denosumab 120 mg SC in order to control the hypercalcemia along with, cautious intravenous hydration. Within one week after Denosumab therapy, serum corrected calcium decreased to 3.07 mmol/L. After another week, corrected calcium reached 2.53 mmol/L. When his urine output improved further and his calcium levels dropped, hemodialysis was discontinued. His calcium level later normalised to 2.49 mmol/L.
After ruling out the common differential of PTH independent hypercalcemia, and from the diuretic phase the patient went through with concomitant hypercalcemia following hypocalcaemia, it was concluded that the cause of hypercalcemia was rebound hypercalcemia following rhabdomyolysis recovery.
Conclusion: hypercalcemia can complicate the recovery phase of rhabdomyolysis. Careful monitoring of calcium levels and management are warranted.
References:
[1] Mohsin N, Budruddin M, Pakkyara A. Calcium Kinetic in a Patient with Acute Renal Failure due to Rhabdomyolysis: A Case Report and Review of Literature. Oman Medical Journal. 2010;25:324–326.
SAT-012 Screening for Gestational Diabetes Mellitus: Universal or Selective Screening? Screening for Gestational Diabetes Mellitus: Universal or Selective Screening?
Authors: Okunowo Bolanle Olajumoke , Fasanmade Olufemi A , Odeniyi Ifedayo A , Ohwovoriole Augustine E 
Published: May 2020

Abstract
Screening for gestational diabetes mellitus: universal or selective screening?
Introduction:
The presence or absence of risk factors is often employed in screening for Gestational Diabetes Mellitus (GDM). The risk factors for GDM includes previous delivery of macrosomic babies, family history of type 2 diabetes mellitus, previous GDM among others. The impact of selective screening is yet to be fully evaluated in our environment.
Objective
To determine the impact of selective screening on diagnosis of gestational diabetes mellitus
Methods
The study was a prospective open cohort study carried out from 1st March to 30th November 2017 at the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria. Ethical approval was obtained from the Health Research Ethics Committee of Lagos University Teaching Hospital (LUTH) before commencement of the study
All the pregnant women were categorized into either risk group or control group based on the presence or absence of clinical risk factors for GDM. All participant had 75g Oral Glucose Tolerance test (OGTT) done at 24 to 28 weeks gestation and follow up till delivery.
The data obtained were age, risk factors for GDM, fasting plasma glucose, one-hour post glucose load plasma glucose & two-hour post glucose load plasma glucose. The data were presented as mean, standard deviation, percentages & chi square. The p value ≤ 0.05 was considered significant
Results
Ninety pregnant women were screened for GDM. Forty-four women had risk factors for GDM while 46 were non risk group. Their mean age was 32.6± 5 years. The mean age for the risk & non-risk group were similar.
The overall prevalence of GDM using the IADPSG criteria was 23.3%. The percentage of women in the risk group with GDM was 38.6% while those women in the non risk group with GDM was 8.7% which was statistically significant (p value 0.004).
Discussion
The most commonly identified risk factors for GDM in this study were family history of type 2 diabetes mellitus, history of unexplained miscarriage & previous history of delivery of macrosomic babies.
Some women in the non-risk were diagnosed, even though the prevalence was lower than that observed among women with risk factors for GDM. Approximately one in ten women would have been missed if selective screening was employed in this study.
Most of the women in the non-risk group who were diagnosed with GDM were managed with medical nutritional therapy while majority of women in the risk group had insulin therapy.
Conclusion
The findings in our study further supports the idea of universal screening for GDM in order to avoid missed diagnosis.
Keywords: gestational diabetes mellitus, Screening, oral glucose tolerance test
SAT-277 A Fierce Presentation of Cushing Disease
Authors: Al Sabie Farah Laith , Jain Meenu , Aziz Ammara 
Published: May 2020

Abstract
Introduction: Cushing disease refers to the endogenous overproduction of glucocorticoid due to an ACTH-producing pituitary adenoma. It is important to recognize and treat due to the adverse health outcomes associated with it. We describe an unusual case of Cushing disease which presented very rapidly and progressively with extremely high cortisol levels mimicking those seen in ectopic production of ACTH.Case Presentation: A 43 year old Caucasian man, with no past medical history, presented with hypertensive crisis. He was discharged home with anti-hypertensive medications. Over the next 4 months, he gained 20 pounds, mainly around his abdomen, developed fatigue, and blood pressure continued to be high despite six anti-hypertensive medications, developed diabetes and hypokalemia, requiring 120 meq/day of potassium chloride. On exam, he had plethora, central obesity and wide, purple striae over his abdomen. Work-up for secondary causes of hypertension showed normal renal Doppler US, normal aldosterone and renin activity, normal plasma metanephrines, however, his 24 hour urinary free cortisol was dramatically elevated at 4022ug/day with a urine volume of 4 L, 1 mg dexamethasone suppression test showed unsuppressed serum cortisol of 55ug/dl. Morning ACTH of 125 pg/ml with concurrent serum cortisol level of 53.8 mcg/dl, indicated ACTH-dependent hypercortisolism. Inferior petrosal sinus sampling indicated a pituitary source of ACTH. Sellar MRI initially did not show a pituitary adenoma, however, repeat MRI with a 3-Tesla magnet showed a 4 mm pituitary adenoma. He was treated with ketoconazole and was started on atovaquone for PCP prophylaxis while awaiting trans-sphenoidal resection, which he had a month later. Pathology showed a 4 mm adenoma which stained strongly for ACTH. On postoperative day 1, serum cortisol dropped to 2.1 from 52.3 mcg/dl, and patient was discharged on hydrocortisone replacement. Three weeks later, he had lost 12 pounds, hyperglycemia improved with discontinuation of insulin, hypokalemia resolved and hypertension was well controlled on two anti-hypertensives. Discussion: ACTH-dependent Cushing syndrome is either caused by Cushing disease, or from ectopic ACTH production from a tumor. Cushing disease is characterized by a gradual onset and subtle manifestations of hypercortisolism. Acute, severe presentation favors an ectopic ACTH producing tumor, and is associated with much higher cortisol levels. In our patient, clinical data suggested ectopic ACTH production, yet he was found to have Cushing disease, and was treated successfully with trans-sphenoidal resection of the pituitary adenoma. It is imperative to consider all possibilities, and do the full work up so as not to miss an atypical presentation of Cushing disease, and direct treatment accordingly.