bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSUN28 Factors Associated with False-positive Fractionated Metanephrines in Plasma and Urine
Authors: Yu Kai , Young William F , Achenbach Sara , Atkinson Elizabeth , Singh Ravinder , Grebe Stefan , Bancos Irina 
Published: November 2022

Abstract

Context
Plasma and 24-hr urine metanephrine (M) and normetanephrine (NM) are the standard of care tests used in the biochemical diagnosis of pheochromocytoma and paraganglioma (PPGL). Considering the rarity of PPGL, false positive (FP) results represent a challenge because they lead to additional investigations, healthcare burden, and uncertainty for the patient. The impact of medications on the rate of FP results is not fully established.

Objective
We aimed to identify the medications associated with the FP rate of 24-hr urine and plasma M and NM measured by the HPLC-MS/MS method.

Methods
We conducted a single-center study of patients who had 24-hour urine or plasma M and NM testing between 09/27/2015 and 02/15/2021, and who had a follow-up of at least 6 months. Results were considered FP if M/NM were &gt; upper limit of the normal ranges (ULN) and there was absence of PPGL. Results were considered true negative (TN) when M/NM were within the reference ranges in patients without PPGL. Age- and sex-adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression models.

Results
Plasma M/NM testing was performed in 3152 patients and 24-hr urine M/NM was performed in 2008 patients. The FP rate for the M fraction (plasma: 0.8%, urine: 1.3%) was much lower than the FP rate for NM (plasma: 16%, urine: 4.4%); thus, the impact of medications on FP rate was examined only for NM. In those with FP NM, the median degrees of elevation were 24% (IQR 10-46) &gt;ULN in plasma and 26% (IQR 11-45) &gt;ULN in urine.
When compared to patients with TN results, patients with FP plasma NM were more likely to be treated with opioids (OR=1.29, 95%CI, 1.04-1.60), tricyclic antidepressants (OR=1.61, 95%CI,1.14-2.27), serotonin–norepinephrine reuptake inhibitors (OR=1.85, 95%CI, 1.35-2.53), second generation antipsychotics (OR=2.32, 95%CI, 1.28-4.20), but not first generation antipsychotics (OR=1.23, 95% CI, 0.86-1.75) when compared to the TN group.
When compared to patients with TN results, patients with FP urine NM were more likely to be treated with opioids (OR=1.96 95%CI, 1.26-3.06), tricyclic antidepressants (OR=2.61, 95%CI, 1.47-4.65), serotonin–norepinephrine reuptake inhibitors (OR=2.20, 95%CI, 1.20-4.02), and both first (OR=3.06, 95%CI, 1.74-5.38) and second generation antipsychotics (OR=2.51, 95%CI, 1.03-6.13).

Conclusion
The plasma NM FP rate was 16% and 3-fold higher than the same measurement in urine (4.4%). Several classes of medications had a significant impact on the rate of FP NM. Clinicians should consider use of 24-hr urine M and NM in low suspicion cases of PPGL where the diagnosis simply needs to be excluded.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF21 | PSAT76 Epigenetic Programs Stabilize a Differentiated Cell State Required for Sustained Proliferation in Adrenocortical Carcinoma
Authors: Mohan Dipika , Borges Kleiton , Finco Isabella , LaPensee Christopher , Rege Juilee , Little Donald , Else Tobias , Almeida Madson , Latronico Ana Claudia , Mendonca Berenice , Auchus Richard , Rainey William , Marie Suely , Giordano Thomas , Venneti Sriram , Candida Fragoso Maria , Breault David , Lerario Antonio , Hammer Gary 
Published: November 2022

Abstract
Adrenocortical carcinoma (ACC) is a rare, aggressive, and poorly understood cancer of the adrenal cortex. Abnormal epigenetic patterning is a major predictor of dismal disease outcomes. Patients with genome-wide CpG island hypermethylation (CIMP-high) experience rapidly recurrent and routinely fatal disease. A deeper understanding of how epigenetic programs coordinate tumorigenesis is essential to develop improved medical therapies. We identify that DNA hypermethylation is directed to targets of a histone modifying complex, PRC2, suggesting cross-talk between DNA and histone methylation in CIMP-high ACC. In contrast to our expectations, we discovered that DNA methylation and PRC2-directed histone methylation are mutually exclusive. Additionally, we identified that EZH2 (a canonical member of the PRC2) forms a separate complex with tissue-specific proteins to coordinate sustained proliferation and steroidogenic differentiation in vitro and in vivo. These complexes persist through advanced stages of human malignancy and are conserved in mouse models of adrenal carcinogenesis. Taken together, our studies illustrate how CpG island hypermethylation exposes a pharmacologically targetable tissue-specific therapeutic vulnerability, and stabilizes a differentiation state required for sustained proliferation. Ultimately, we hope this work illuminates novel strategies for tissue-specific disruption of the aberrant epigenetic wiring supporting this devastating disease.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:24 p.m. - 1:30 p.m.
RF21 | PSUN08 Morphologic or Molecular Imaging - Diagnostic Capabilities in von Hippel-Lindau related pheochromocytoma
Authors: Patel Mayank , Jha Abhisek , Ling Alexander , Chen Clara C , Millo Corina , Talvacchio Sara , Ezemobi Josephine , Kailah Charles , David Taïeb , Carrasquillo Jorge A , Pacak Karel 
Published: November 2022

Abstract

Background
Within a spectrum of cancers implicated by VHL germline pathogenic variants, one rare cancer which may present in patients are pheochromocytomas (PHEOs). These tumors occur in the adrenal glands and predispose patients to a variety of morbid clinical symptoms due to the excess secretion of catecholamines. As a part of these patients’ management, imaging is important to localize the tumors of which there are both morphologic (CT and MRI) and molecular (PET/CT with 18F-FDG, 68Ga-DOTATATE, 18F-DOPA, and 18F-DA) imaging modalities.

Purpose
To determine which imaging modalities provided the optimal detection of VHL-related PHEO.

Methods
The study compared detection of 19 PHEOs (18 histologically proven and 1 is a contralateral tumor awaiting resection) in 12 patients. The CT and MRI were evaluated by a body radiologist and the PET/CT of18F-FDG, 68Ga-DOTATATE, 18F-DOPA, and 18F-DA were evaluated by a nuclear medicine physician in a blinded fashion. Both experts graded using a five-point Likert scale (1 – not PHEO and 5 – PHEO). For analysis, the Likert scale was dichotomized with 1-3 designating negative for PHEO and 4-5 positive for PHEO. The findings were reported as detection rates of positive PHEOs found on imaging to the gold standard of pathologically (aside from one contralateral PHEO awaiting surgery) proven PHEOs. The McNemar test was performed to compare the statistical relevance of detection rates between histology and the imaging modalities. Two-sided p values &lt;0.05 were considered significant.

Results
The detection rates were CT 17/19 [89.5%, 95% CI = 66.9%-98.7%], MRI 17/17 [100%, 95% CI = 80.5%-100%], 18F-FDG PET/CT 16/17 [94.1%, 95% CI = 80.5%-100%], 68Ga-DOTATATE 5/9 [55.6%, 95% CI = 21.2%-86.3%], 18F-DOPA 12/14 [85.7%, 95% CI = 57.2%-98.2%], and 18F-DA 4/6 [66.7%, 95% CI = 22.3%–95.7%]. All McNemar tests showed p-values greater than 0.05, which were not statistically significant.

Conclusion
The study was performed in a small patient set with VHL-related PHEO showed MRI, with the highest detection percent followed by 18F-FDG PET/CT. More trials with a larger patient set are needed to support the statistical relevance as it was not seen in this study. Furthermore, performing a study on a patient cohort with additional VHL associated cancers could prove clinically beneficial for patients.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:18 p.m. - 1:23 p.m.
RF33 | PSAT68 Gonadotropin-Releasing Hormone Agonist Therapy Does Not Affect Bone Mineral Density in Congenital Adrenal Hyperplasia: a Clinical Study
Authors: Flokas Myrto , Kollender Sarah , Wakim Paul , Sinaii Ninet , Parker Megan , Mallappa Ashwini , Merke Deborah 
Published: November 2022

Abstract

Background
Children with congenital adrenal hyperplasia (CAH) are at risk for early central puberty, and gonadotropin-releasing hormone analogs (GnRHa) are frequently used aiming to improve adult height. However, their effect on bone health among the CAH population has not been previously studied. GnRHa reduce sex steroid levels and delay central puberty, which may negatively affect the achievement of peak bone mass. In healthy children, bone mass increases with time, reaching its peak between the second and third decades of life. The purpose of this study was to investigate the short-term and long-term effect of GnRHa therapy on the bone mineral density (BMD) of patients with classic CAH.

Methods
Sixty patients with classic CAH due to 21OH deficiency were followed longitudinally at our institution with DXA scans at the time they achieved adult height. Adult height was considered attained when bone age exceeded 15 years in girls and 17 years in boys. Twenty-one patients treated with GnRHa (81% male, 57% salt wasting, treated for mean ± SD: 4.3 ±2 years) were compared to 39 patients not treated with GnRHa (49% male, 79.5% salt wasting). BMD z scores, adjusted for height and age, were evaluated at the time they reached adult height and on average 8.3 years later.

Results
There was no difference between GnRHa groups in total body (p=0.96), femoral neck (p=0.24), lumbar spine (p=0.59), forearm (p=0.38), and total hip (p= 0.31) z scores at adult height attainment. In multivariable analyses, there was no effect of GnRHa on BMD z scores at any site. In reduced models, increased 17-hydroxyprogesterone (17-OHP) levels correlated with higher BMD z scores for total body (p=0.003), lumbar spine (p&lt;0.001), and forearm (p&lt;0.001). Higher BMI (p=0.014) and no treatment with dexamethasone (p=0.022) were also associated with higher femoral BMD z score. Overall, the follow up DXA during young adulthood (n=28) showed significant decreases in z scores at total body (p=0.019), femoral neck (p=0.036), lumbar spine (p&lt;0.001), forearm (p&lt;0.001), and total hip (p=0.024), and use of GnRHa did not contribute. Interestingly, when adjusting for midparental height, those treated with GnRHa had lower adult height z scores than those without GnRHa (p=0.037).

Conclusion
Treatment with GnRHa for approximately 4 years does not impact BMD in adolescents and young adults with CAH, and exposure to adrenal androgens may play a protective role. In patients with CAH, BMD decreases with time and during the second and third decades of life, which may reflect the effect of long-term supraphysiologic glucocorticoid therapy. Although intended to preserve height, children with CAH who experience early puberty have loss of adult height, despite treatment with GnRHa.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:54 p.m. - 12:59 p.m.
RF33 | PSUN03 Rates of Pheochromocytoma/Paraganglioma Screening in At-Risk Populations
Authors: Grigoryan Seda , Nhan Winnie , Zhang Lei , Urban Caitlin , Holevinski Lynn , Zhao Lily , Turcu Adina 
Published: November 2022

Abstract

Background
Hypertension is estimated to affect 1: 2 adults in the USA, and secondary hypertension accounts for up to 40% cases. Pheochromocytomas and paragangliomas (PPGL) are thought to be rare causes of hypertension, although their true prevalence might be underestimated. Less than half of patients with PPGL have prototypical symptoms. PPGL can lead to serious complications, including death, particularly if unrecognized. Expert guidelines recommend screening for secondary causes of hypertension in patients with resistant hypertension, patients with early-onset hypertension, and in those with hypertension and an adrenal mass. The rates of PPGL screening are unknown.

Objective
To evaluate the rates and patterns of PPGL screening among candidate patients.

Methods
We conducted a retrospective review of adult patients (age ≥ 18 years) with hypertension seen in a university-based outpatient setting between 01/01/2017 - 06/30/2020, and we included patients with: 1) resistant hypertension (uncontrolled hypertension while taking at least 3 antihypertensive agents OR taking ≥4 antihypertensive agents); 2) hypertension at age &lt;35 years; 3) adrenal nodule(s). We excluded patients with renovascular hypertension, advanced chronic kidney disease (CKD stage ≥4), stage III and IV heart failure, adrenal insufficiency, and congenital adrenal hyperplasia.

Results
Of 203,535 patients with hypertension, 71,088 (35%) met at least one of the above criteria, and only 2013 (2.83%) were screened for PPGL. Overall, patients screened were younger (56.2 ± 17.4 vs. 63.9±17.1 years, p &lt;0.001), more often women (54.1% vs. 44.2%, p=0.001), and non-smokers (54.6% vs. 47.5%, p&lt;0.001) than those not screened. While most patients included in the study were white (80%), the proportion of black patients was larger among those screened (19.9% vs.13.3% of those not screened, p&lt;0.001). Of the three indications for PPGL screening, the rates were highest in patients with hypertension and adrenal nodule(s) (51.7%), while patients with early onset hypertension and those with resistant hypertension were rarely screened (3.9% and 2.4%, respectively). Multivariable logistic regression with LASSO selection showed that the odds of PPGL screening were higher in black vs. white patients (1.35 [1.19-1.53]); those who never smoked (1.68 [1.41-2.00]); patients with stroke (1.34 [1.16-1.54]); dyslipidemia (1.41 [1.26-1.57]), CKD (1.40 [1.26-1.56); obstructive sleep apnea (1.96 [1.76-2.19]); and adrenal nodules (55.1 [44.53-68.17]).

Conclusions
Screening for PPGL is conducted in roughly half of patients with adrenal nodules and hypertension, but rarely in patients with resistant or early onset hypertension. Screening occurs more often in patients with complications known to be associated with PPGL, including cardiovascular accidents.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
LBODP018 Hypercalcemia In A Child On Ketogenic Diet For Intractable Epilepsy
Authors: Gurnurkar Shilpa , Gafen Noah , Carakushansky Mauri , Vyas Neha 
Published: November 2022

Abstract

Introduction
Ketogenic diets have been shown to significantly reduce seizures in patients with intractable epilepsy refractory to common antiepileptic medications. There have been reports of hypercalcemia in diet-controlled epilepsy patients. The exact cause of hypercalcemia in ketogenic diets is unclear but decreased bone formation and impaired calcium excretion are suggested mechanisms.

Case
An 8-year-old male with Lennox-Gastaut syndrome was noted to have incidental hypercalcemia on admission (serum calcium 11.5 mg/dL, n = 8.8-10.1) for aspiration pneumonia, UTI, and increased seizure-like activity. Hypercalcemia persisted throughout his hospitalization (range: 10.8-12.4 mg/dL). Evaluation of hypercalcemia indicated normal serum phosphate (5.6 mg/dL, n = 3. 0-6. 0), appropriately low PTH (9.5 pg/mL, n = 10. 0-65. 0), undetectable PTHrP (&lt;2. 0 pmol/L), low 25 (OH) vitamin D (19ng/ml, n=30-100), low 1,25 (OH)2 vitamin D (7.1 pg/mL, n = 19.9-79.3), normal creatinine (0.3 mg/dL, n = 0.31-0.61), slightly elevated TSH (5.13 mIU/L, n = 0.5-4.5) with a normal free T4 (1.4 ng/dL, n = 0.8-2. 0), and physiologic CBC. Alkaline phosphatase was low (88 U/L, n = 156-386) and skeletal survey showed diffuse demineralization. Urine calcium creatinine ratio was elevated at 0.6 when serum calcium was 11.6 mg/dl. Patient was 7 months into a ketogenic diet that successfully reduced seizure frequency and the plan was to further intensify the diet. On hospital day 11 when serum calcium was 12mg/dl, he was started on IV normal saline and furosemide up to a daily dose of 60 mg. On hospital day 12, patient was started on calcitonin (3 U/kg twice daily SQ). Serum calcium normalized (10 mg/dl), but calcitonin had to be discontinued due to severe nausea and vomiting. GI symptoms did not improve on a lower calcitonin dose. Calcium gradually corrected on fluids and furosemide, but hypercalcemia recurred (11mg/dl) after furosemide was weaned. The patient was then transferred to a higher level of neurologic care to continue treatment and increase the intensity of the ketogenic diet. There, on cumulative hospital day 26, he received zoledronic acid (0. 0125 mg/kg) which was tolerated well and resulted in normalization of the serum calcium levels (10.9mg/dl, 10.2mg/dl and 9.8mg/dl on days 26, 28 and 29 respectively).

Conclusions
This case adds to the limited literature available on the evidence that management of refractory epilepsy with ketogenic diets may cause acute hypercalcemia. Although the underlying cause is unclear, decreased osteogenesis as marked by low alkaline phosphatase activity remains the likely explanation. Other risk factors such as immobilization also need to be explored. The successful implementation of protocols used to treat our patient and similar patients in the literature may help create screening protocols for early detection and management of the hypercalcemia to prevent complications.
Presentation: No date and time listed
LBODP065 Rare Cause Of Bone Pain In MEN Syndrome
Authors: Ramdhanie Lisa Indira , Pinsker Richard , Cervellione Kelly 
Published: November 2022

Abstract
Introduction: MEN 1 syndrome is a rare disease in children and young adults, with prevalence reported as 2 per 100,000. MEN 1 caused by mutations in the MEN1 tumor suppressor gene, characterized by 2 or more MEN1 tumors: parathyroid, anterior pituitary, pancreatic islet tumors. To the best of our knowledge, osteomyelitis of the pelvis has not been reported as a complication in the literature in patients who were diagnosed with MEN1Case21 yo male from Honduras with PMHx of remote asthma presented with a common complaint of abdomen pain but found to have a rare diagnosis. He had 2 days of lower abdomen pain associated with non-bilious non bloody vomiting. Initial were significant for calcium 12.9, phosphorus 1.5 magnesium 1.8 and PTH 360. 4 mm renal stone 4 mm was detected on CT abdomen/pelvis. The initial EKG demonstrated J point elevation due to the hypercalcemia. He was admitted to the PICU for continuous telemetry monitoring due to the abnormal EKG related to electrolyte abnormalities. Hypercalcemia treatment was initiated with aggressive hydration, calcitonin administration as well as zoledronic acid administration. The patient's calcium levels improved as well as EKG. The parathyroid scan was positive for a right-sided parathyroid adenoma. He underwent right Inferior Parathyroidectomy, Intraoperative Nerve Monitoring, Cryopreservation of Parathyroid Tissue. As part of his diagnostic work-up for hyperparathyroidism, he was screened for MEN. His pituitary function was abnormal: ACTH and cortisol levels were high, his testosterone and gonadotropins were inappropriately low as well as TSH and T4. A microadenoma was present on brain MRI. No Pancreatic Neuroendocrine Neoplasia was found. The diagnosis of MEN 1 was made. Despite the improvements in his endocrinopathies, he continued to have lower abdomen pain associated with intermittent fevers. He was seen by urology and orthopedics. Initially MRI demonstrated bone erosion thought to be secondary to hypercalcemia but repeat MRI imaging of the pelvis was suspicious for phlegmon vs. developing abscess secondary to osteitis pubis. His blood cultures were positive for MSSA. He was started on antibiotics with continued clinical improvementThis patient presented with one of the most common complaints in the ED, abdomen pain and was found to have two rare and potentially fatal diagnosis which was identified and treated with a good clinical outcome Discussion: This case highlights a rare disease in the setting of osteomyelitis which could easily be missed as a manifestation of bone pain from hypercalcemia. The patient did experience fevers and malaise that was initially attributed to zoledronic acid administration. When his pain did not resolve MRI found osteomyelitis, allowing early antibiotic administration and prevention of sepsis.
Presentation: No date and time listed
LBSAT130 Hypercalcemia In Pregnancy Due To CYP24A1 Mutation
Authors: Agu Chinyere , Cho Ei , Resta Christine , Luba Rakhlin 
Published: November 2022

Abstract

Background
The active form of vitamin D (1,25 OH2 vitamin D) is catabolized by a key enzyme 1,25 OH vitamin D-24 hydroxylase, which is encoded by the CYP24A1 gene. Loss of function mutation in the CYP24A1 leads to elevated levels of active vitamin D, causing PTH independent hypercalcemia with nephrolithiasis and nephrocalcinosis. Two phenotypic variants have been identified: idiopathic infantile hypercalcemia, which is a more severe form presenting in infancy, and a milder form with onset in adulthood as is this case. Pregnancy is known to initiate or worsen the hypercalcemia.

Clinical Case
A 27-year-old woman presented at 11 weeks gestation with hyperemesis, noted to have hypercalcemia calcium 15.7mg/dl (8.2 to 10.1 pg/ml), low PTH 2pg/ml (24 -85 pg/ml) with high serum 1,25 OHD 309pg/ml (nl 19.9-79.3 pg/ml). She had low PTHrp, normal ACE level, and negative TB testing. Pre-pregnancy calcium was normal (9.8mg/dl). She had a history of hypercalcemia in previous pregnancy (Calcium 13mg/dl) that ended in IUFD. Family history revealed nephrolithiasis in her sister, mother, and paternal aunt as well as a consanguineous marriage in our patient and her parents. Vitamin D metabolites evaluated via liquid chromatography showed low serum 24,25(OH)2D (0.29ng/ml nl N/A) and elevated 25OHD 138 ng/mL (20-80 ng/ml). Ratio of 25 (OH) Vit D to 24,25(OH)2D was 475.86 (values &gt;80 indicate probable bi-allelic CYP24A1 deletion or mutation. Genetic test pending.

Conclusion
This case highlights the fact that patients with 24 hydroxylase deficiency may be normocalcemic with hypercalcemia unveiled during pregnancy due to increased 1alpha hydroxylase production by the placenta and kidneys as well as intake of prenatal vitamins containing calciferol. An index of suspicion for CYP24A1 mutation is needed in patients with high active vitamin D metabolites, high or normal calcium, low PTH, family history of kidney stones or worsening hypercalcemia in pregnancy.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.