bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-120 Humoral Hypercalcemia of Malignancy Caused by Squamous Cell Carcinoma of the Penis
Authors: Kanta Romana , Ansari Mohammad Jamal Uddin , Ali Mariam , Rehman Anis , Jabri Hadoun , Parveen Sanober , Jakoby Michael G 
Published: May 2020

Abstract
Background. Humoral hypercalcemia of malignancy (HHM) accounts for approximately 80% of hypercalcemia associated with cancer. We present an unusual case of HHM caused by recurrent squamous cell carcinoma of the penis. Case. A 45 year old male was brought to the emergency department (ED) due to worsening confusion over 48 hours. History was notable for squamous cell carcinoma of the penis initially diagnosed 12 years ago and managed by partial penectomy and ilioinguinal lymphadenectomy. Recurrence had been diagnosed approximately 30 days before presentation to the ED. The patient was somnolent, disoriented, and unable to follow commands. Admission laboratories were remarkable for new occurrence of hypercalcemia (serum calcium corrected for low albumin 17.0 mg/dL, 8.6–10.3) and acute renal failure (Cr 1.7 mg/dL, 0.6–1.3; BUN 44 mg/dL, 7–25). No masses or hemorrhages were observed on head imaging, though computed tomography of the chest, abdomen, and pelvis revealed multiple lung and liver masses and lytic bone lesions. Biopsy of a rib mass confirmed metastatic squamous cell carcinoma. Intact PTH level was suppressed at 1 pg/mL (12–88), but parathyroid hormone related protein (PTHrP) was significantly elevated at 120 pM (0.0–2.3). HHM due to PTHrP was diagnosed. Corrected calcium level reached a nadir of 9.5 mg/dL on hospital day seven after saline hydration, calcitonin, and zoledronic acid, but high dose denosumab (120 mg weekly) was started hospital day 10 after corrected calcium level increased to 11.7 mg/dL. Despite corrected calcium levels consistently in the range of 10.5–11.5 mg/dL for the remainder of hospitalization, the patient’s mental status failed to improve. He expired on hospital day 24. Conclusions. Squamous cell carcinoma of the penis is rare in the United States, with only about 2,000 cases diagnosed annually. Though squamous cell carcinomas are collectively the most common cause of PTHrP-related hypercalcemia, there are only a few cases of PTHrP-related hypercalcemia due to squamous cell carcinoma of the penis documented in the peer reviewed literature. As in our patient’s case, other penile carcinoma patients with PTHrP-related hypercalcemia have had regionally advanced or metastatic disease and limited therapeutic response to bisphosphonates. Our patient’s survival after occurrence of hypercalcemia was also similar to other published cases of penile carcinoma complicated by PTHrP-related hypercalcemia. This case confirms the potential for penile carcinoma to cause HHM through hypersecretion of PTHrP like squamous cell carcinomas of the lung, head, and neck. Denosumab may be a more effective treatment option than a bisphosphonate based on the therapeutic experience in this case and others. PTHrP-related hypercalcemia appears to be a strong indicator of limited life expectancy for penile carcinoma as for other malignancies.
MON-920 Pediatric Parathyroid Carcinoma Presenting With Acute Progressive Genu Valgum
Authors: Hu Tina Y , Berman Loren , Parkes William J , Franzone Jeanne M , Mody Tejal , Conard Katrina , Gannon Anthony W 
Published: May 2020

Abstract
BACKGROUND: Parathyroid carcinoma (PC) is exceptionally rare in children and its clinical features are poorly understood. Available reports have identified that very high serum calcium and parathyroid hormone levels would be expected in this disease. Definitive therapy for PC requires en bloc resection of the parathyroid tumor to reduce the risk of disease recurrence. Unfortunately, there are very few treatment options for metastatic PC and patients with recurrent PC have a high risk of mortality related to their disease. Because of the rarity of the condition, there are very limited data including pediatric patients.
Case: A previously healthy 13-year-old girl initially presented to primary care with bilateral foot and ankle pain in the context of acute and progressive genu valgum, referred to the orthopedic clinic. Lab evaluation prompted by imaging demonstrated severe hypercalcemia (15.6 mg/dL) and hyperphosphatasia (Alkaline phosphatase 2056 units/L). She was urgently referred to our clinic where we found her to have a firm right sided neck mass within the thyroid. Lab testing at that time confirmed profound hyperparathyroidism (PTH 2970 pg/mL). Neck ultrasound confirmed the presence of a 5.8 cm hypoechoic lesion adjacent to the right lower lobe of the thyroid. The patient received IV fluid resuscitation before undergoing urgent parathyroid surgery. The parathyroid lesion was grossly adherent to the thyroid gland and she received en bloc resection of the tumor and right lobe of the thyroid. Post-operatively, PTH rapidly declined to &lt;3.4 and she developed a prolonged hypocalcemic phase. PTH function improved, but she continued to require high doses of calcium carbonate to address hungry bone syndrome over subsequent weeks. Comprehensive evaluation included testing for genetic mutations, deletions, and duplications in CASR, CDC73, CDKN1B, MEN1 and RET, all of which were negative. Extensive genetic testing of the parathyroid tumor did not identify any specific mutations which have been previously associated with PC. Six months post-operatively, her labs have vastly improved, although she has clinical evidence of PTH resistance and her alkaline phosphatase has not yet normalized. Neck ultrasound, F-18 FDG PET/MRI imaging and Sestamibi scans show no evidence of persistent disease.
Conclusions: While parathyroid carcinoma is extremely rare in pediatric patients, the diagnosis must be considered in cases of hypercalcemia with marked elevations in PTH and palpable neck mass. Although rarely described, bone changes related to PC may be dramatic and may result in lasting morbidity - including genu valgum requiring surgical intervention as well as prolonged hungry bone syndrome and metabolic bone disease. Genu valgum is a unique pediatric feature of this disease because this may only evolve in individuals whose physes are open.
SAT-688 Rare Case of 48 XXYY Syndrome with Suspected Type 1 Diabetes Mellitus
Authors: Aftab Hassaan B , Mirza Faryal Sardar 
Published: May 2020

Abstract
BACKGROUND: 48 XXYY syndrome is a rare aneuploidy characterized by the presence of an extra X and Y chromosome in males. Patients share features of Klinefelter syndrome such as tall stature, hypogonadism, congenital malformations and neurocognitive issues. Hypogonadism may cause abdominal adiposity hence increasing risk of insulin resistance and type 2 diabetes mellitus (DM). Klinefelter syndrome has been associated with certain autoimmune diseases however there is no autoimmune disease link described with XXYY syndrome. We present a patient with XXYY polysomy with insulin requiring DM.Clinical Case: A 26-year-old intellectually disabled male with history of XXYY polysomy presented with seizures and was evaluated for DM management. At age 18, he was noted to have hyperglycemia while undergoing dental extractions for brittle enamel leading to the diagnosis of DM. He was initiated on oral medications for a short period of time and transitioned to insulin due to significant hyperglycemia. Endocrine evaluation at the time also revealed hypergonadotropic hypogonadism and evaluation for Klinefelter syndrome revealed 48 XXYY aneuploidy.Patient’s history was significant for poorly controlled hyperglycemia with HbA1C ranging in 12–14% range in the last few years. History was negative for diabetic ketoacidosis (DKA) as per his primary endocrinologist, despite being noncompliant with his insulin therapy. History was negative for retinopathy, nephropathy or macrovascular complications, although he did have distal extremity paresthesia. On exam, he was noted to be edentulous with tall stature, BMI 21.7, facial dysmorphism, pes planus and 5th-digit clinodactyly bilaterally. Family history was positive for type 2 DM in father and prediabetes in mother.He presented with seizures and was diagnosed with brain abscess. Hyperglycemia was initially managed with IV insulin, followed by basal/bolus therapy. Fasting labs 20 hours after receiving insulin glargine showed glucose of 284 mg/dL, C-peptide 0.6 ng/mL (ref range: 0.8–3.5), proinsulin less than 1.6 pmol/L (less than 8.0), insulin 4 uIU/mL (3–19) suggestive of type 1 DM. Anti-GAD65 and anti-ICA antibody levels were negative. Additional antibody evaluation for type 1 DM (islet antigen 2, insulin autoantibody, micro-insulin and zinc transporter 8) is currently pending at the time of writing.Conclusion: Prevalence of XXYY syndrome is 1:18 000–1:40 000 in males. There are few case reports describing the association of type 2 DM with this syndrome. Our patient’s low BMI, low insulin and C-peptide with hyperglycemia indicate type 1 DM, although the absence of DKA in the setting of noncompliance suggests residual beta cell function or maturity onset diabetes of the young (MODY). Neither T1DM nor MODY has been reported with 48XXYY previously. Clinicians should be aware of this association as it has implications in terms of management of DM.
SUN-720 LC-MS/MS Measurements of Parathyroid Hormone-Related Protein (PTHrP): Association Between Ca, PTH and PTHrP in Clinical Samples
Authors: Kushnir Mark M , Straseski Joely A 
Published: May 2020

Abstract
Parathyroid hormone related protein (PTHrP) is involved in intracellular calcium (Ca) regulation and homeostasis. The main clinical utility of PTHrP as a biomarker is to assist with determining the cause of unexplained hypercalcemia (UH). Considering that PTHrP, along with parathyroid hormone (PTH), is involved in Ca homeostasis, we evaluated associations between concentrations of Ca, PTH, PTHrP and age, and the between-sex differences in clinical patient samples. We reviewed historic data on Ca, PTH and PTHrP concentrations measured in routine patient samples (n=2,701) submitted for testing to a large clinical diagnostic laboratory. Among the analysed samples 31.1% were from adults (18-59y), 52.9% from older adults (60-79y) and 16.9% from elderly (&gt;79y). Out of the samples, 60.5% were from women (W) and 39.5% from men (M). PTHrP was measured using a validated LC-MS/MS method; Ca and parathyroid hormone (PTH) were measured using the Cobas 8000 (Roche). The imprecision of all assays was &lt;10%. Reference intervals (RI) for PTHrP were &lt;3.3 pmol/L and &lt;2.2 pmol/L in W and M, respectively; RI for calcium was 8.4–10.2 mg/dL, and for PTH was 15–65 pg/mL. Median (mean) PTHrP concentrations in samples from adults, older adults and elderly were 1.5 (7.9), 2.5 (8.7) and 3.2 (5.3) pmol/L, respectively. Median (mean) concentrations in samples from W and M were 2.4 (6.3) and 2.5 (10.4) pmol/L, respectively. Statistically significant difference in PTHrP concentrations was observed between W and M from adult (p=0.0005) and older adult (p=0.0038) groups; between W from adult and elderly groups (p=0.0113); and between M from older adult and elderly groups (p=0.028). No significant difference among the age groups was observed in concentrations of Ca and PTH. As expected, direct relationship was observed between concentrations of Ca and PTHrP (ρ=0.189, p&lt;0.0001), while inverse relationships were observed between concentrations of Ca and PTH (ρ=-0.393, p&lt;0.0001), and PTH and PTHrP (ρ=-0.226, p&lt;0.0001). Assessment of the distribution of PTHrP concentrations in samples from W (n=472) and M (n=446) with UH (Ca &gt;10.2 mg/dL and PTH&lt; 15 pg/mL), revealed elevated PTHrP concentrations in 35.0% of W and 59.4% of M; with odds ratio for PTHrP as cause of UH of 0.7 and 2.2, in W and M, respectively. Among the study samples, PTHrP concentrations in 29.3% of samples from W and 54.2% of samples form M were above the sex specific RI. The PTHrP positivity rates in adult, older adult and elderly W (M) were 22.1%, 28.2% and 44.2% (41.2%, 58.5% and 70.5%), respectively. We observed higher prevalence of elevated PTHrP concentrations in M than in W, and in older individuals. PTHrP concentrations above the RI were observed in 39.1% of the analyzed samples. Our data suggest that hypercalcemia caused by elevated PTHrP concentrations is more common for pathologic conditions, which have higher prevalence or specific of M.
SAT-512 Thyrotoxicosis Followed by Hypothyroidism Post Total Laryngectomy and Hemithyroidectomy
Authors: Aljehani Faisal , Funke Katalina , Fernandes Jyotika Kanwar 
Published: May 2020

Abstract
BACKGROUND:
Thyrotoxicosis has been described in few case reports after non thyroid neck surgeries but only in one case report after total laryngectomy and hemithyroidectomy. Subacute lymphocytic thyroiditis has been reported in one case post thyroid lobectomy in a patient with thyroid cancer. Total thyroidectomy or lobectomy are common practice as a part of laryngeal cancer treatment.
Clinical Case:
57- year old male with history of laryngeal cancer was admitted for total laryngectomy, bilateral neck dissection, left hemithyroidectomy. Post-operative Day 3 patient reported feeling anxious and palpitations. On exam he had tachycardia up to a heartrate of 150s/min. His baseline TSH, FT4 and Ft3 were all normal one week before the surgery. On the 5th day after the surgery, TSH was undetectable, FT4 was 3.3(range 0.71 - 1.48), while FT3 was normal 2.66 (range 1.71 - 3.7). Thyroglobulin were high (range 2.8 - 40.9) while Thyroglobulin antibodies, anti TPO and TRAB were all normal. Thyroid US was not done because of technical difficulties given the patient neck surgery. The patient had Burch-Wartofsky Point Scale of 35 at that time. He was started on a beta-blocker and heart rate improved to 110-120. Over the next 5 days his FT4 Improved and was normal by day 10 after the surgery. His TSH and Ft4 showed hypothyroidism 6 weeks after the surgery and levothyroxine was started. He was seen 4 months after the surgery with high TSH concerning for medication noncompliance.
Conclusion:
On our review of literature this would be the second case report of a thyrotoxicosis after total laryngectomy and hemithyroidectomy. Unique to our case is the devolvement of hypothyroidism after the initial phase of thyrotoxicosis resolved while in the other case reported in literature the patient did not develop hypothyroidism. Subsequent hypothyroidism in our case could be from underlying subacute lymphocytic thyroiditis or secondary to hemithyroidectomy.
Reference:
1.
Blenke EJ, Vernham GA, Ellis G. Surgery-induced thyroiditis following laryngectomy. The Journal of laryngology and otology. 2004;118(4):313-4.
2.
Choi YS, Han YJ, Yeo GE, Kwon SK, Kim BK, Park YH, et al. Subacute lymphocytic thyroiditis after lobectomy in a patient with papillary thyroid carcinoma: a case report. Journal of medical case reports. 2013;7:3.
SUN-413 Thyroid Stimulating Hormone Levels Amongst Reproductive Age Latinas: Findings from the ELLAS Study
Authors: Ulrich Nicole D , Waldo Anne , Batchelor Jourdin , Valbuena Felix , Bryce Richard , Neff Lisa , Marsh Erica Elizabeth 
Published: May 2020

Abstract
BACKGROUND: National population data on thyroid disease in women comes largely from NHANES. Prior research utilizing data from NHANES 1999-2002 indicated a 3.1% prevalence of hypothyroidism and 0.6% prevalence of hyperthyroidism among reproductive aged women. In this dataset, Mexican Americans had a similar risk of hypothyroidism but a slightly higher rate of hyperthyroidism when compared to non-Hispanic whites. We present data from a prospective cohort study of reproductive aged Hispanic women residing in the United States (US) in order to examine thyroid disease prevalence in this population.
Methods: The Environment, Leiomyomas, Latinas and Adiposity Study (ELLAS) is a prospective NIMHD funded longitudinal cohort study of reproductive age Latinas/Latinx females in Southeast Michigan. Demographic and health data were collected via bilingual interviewers. Height, weight, and body composition were measured by trained staff using a Tanita MC780U scale. Fasting morning venipuncture was performed and samples were collected in a serum separating tube and sent to a commercial lab (Labcorp – Burlington, NC) for TSH electrochemiluminescence immunoassay [normal reference range 0.45-4.5 mIU/L]. The data were analyzed using SAS version 9.4 (Cary, NC).
Results: 516 patients have enrolled in ELLAS and 450 of these have completed the first study visit. Mean age, BMI, and body fat % were 37.7 ± 7.0 years, 29.9 ± 6.8 kg/m2, 36.3% ± 6.6% (mean ± SD) respectively. Reported countries of birth were Mexico (76.2%), US (9.8%), Central America (6.7%), South America (5.6%), and the Caribbean Islands (0.7%). 34 (7.6%) participants reported a pre-existing thyroid condition. Of those, 28 reported they had been treated for a thyroid condition in the past, and 14 were currently taking prescription medication for thyroid disease. TSH levels were available on 418 women. Of those with a known thyroid condition, 6.5% had TSH values &lt; 0.45 and 16.1% had elevated TSH values (&gt; 4.5) at the time of their study visit, compared to 1.7% and 7.4% overall. 0.2% had TSH &gt; 10. Among those without a known history of thyroid disease, 1.3% had TSH &lt; 0.45 and 6.7% had TSH &gt; 4.5 at their visit. BMI, body fat %, and country of birth were not associated with TSH levels, but there was a small yet significant effect of age on TSH (p=0.009).
Conclusion: In this US cohort of Hispanic women of reproductive age, we observed a high prevalence of thyroid dysfunction in those without pre-existing disease. In women with a known thyroid condition, the prevalence of abnormal TSH values was also high, representing both under- and over-treatment with thyroid hormone. Screening for thyroid disease in this population is important and presents a potential opportunity for intervention in an often underserved population.
SAT-653 Exploring the Role of Brown Adipokines on Hepatic Insulin Resistance Using a Microfluidic Organ-On-Chip
Authors: Tanataweethum Nida , Lee Chaeeun , Trang Allyson , Zhong Franklin , Kim Kihwan , Mehta Jhalak , Cohen Ronald Nelson , Bhushan Abhinav 
Published: May 2020

Abstract
The development of insulin resistance (IR) in liver is a key of pathophysiologic response in type 2 diabetes. Although insulin resistance impairs its ability to suppress hepatic glucose production, insulin regulation of lipogenesis is maintained (1). Currently available insulin sensitizers are effective at lowering glucose levels, but have significant adverse effect on weight gain due to triglyceride accumulation, which highlights a need to develop new therapeutic treatment options for type 2 diabetes. Brown adipose tissue (BAT) has been studied as a new target for anti-obesity and type 2 diabetes as BAT stimulation increases energy expenditure, reduces adiposity, and improves insulin sensitivity (2). However, the underlying mechanisms are not completely understood. To identify the role of BAT adipokines on hepatic insulin resistance, we developed an insulin resistant liver organ-on-chip model and then perfused primary mouse brown adipocyte conditioned media through the hepatocytes. Our results demonstrate that IR hepatocytes treated with brown adipocyte - conditioned media restores insulin sensitivity and improves glucose metabolism. This was verified by significantly increased expression of Phospho-Akt (Ser473) and glucose production gene markers (G6pc and PEPCK), lowered glucose production, increased glucose uptake, and increased glycogen synthesis in treated hepatocytes over IR group (p &lt; 0.05). Our results also indicate that brown adipocyte - conditioned media treatment has the potential to suppress lipogenesis in hepatic insulin resistance. This was confirmed by significantly reduced expression of a lipogenesis gene marker (SREPB1) and fatty acid uptake in treated hepatocytes over IR group (p &lt; 0.05). Current efforts are focused towards identifying the BAT adipokine via mass spectrometry. We conclude that BAT-derived endocrine factors could be a potential target for new drug discovery for obesity and type 2 diabetes treatment.
Reference: (1) Langlet et al. Cell. 2017 Nov;171(4):824-835. (2) Subhadraw et al. Am J Physiol Endocrinol Metlab. 2015 Jun;308(12):E1043-E1055.
Nothing to Disclose: NT, CL, AT, FZ, KK, JM, RC, AB
SUN-219 Electron Transport Chain Complex 2 in Mitochondrial Pregnenolone Synthesis
Authors: Bose Himangshu S , Marshall Brendan , Debnath Dilip , Perry Elizabeth W , Whittal Randy M 
Published: May 2020

Abstract
The mitochondrial P450 family of enzymes (SCC), which require the electron transport chain (ETC) complexes III, IV and V, initiate steroidogenesis by cleaving the sidechain of cholesterol to synthesize steroid hormones, an essential component for mammalian survival. SCC is required for full-term gestation, and aberrant expression may cause pseudohermaphroditism, breast cancer or polycystic ovary syndrome. Complex II or succinate dehydrogenase (quinone) is shared with the TCA cycle and has no proton pumping capacity and no known role in steroid synthesis. We now show that succinate is an intermediate metabolite in the TCA cycle and plays a central role physiologically. Specifically, complex II is required for SCC activation, where the proton pump facilitates an active intermediate state conformation at the matrix, so that in the presence of succinate, ATP can add phosphate. A longer intermediate equilibrium state generates a transient stabilization to enhance the binding of phosphate anions in the presence of succinate anions, resulting in higher enthalpy and activity. An inhibition of the processing at the intermediate state stops phosphate addition and activity. We further describe that phosphate circulation brings the molten globule, an intermediate, to an active folded state. This is the first report showing that an intermediate state activated by succinate facilitates ETC complex II interaction with complexes III and IV for metabolism.