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A Novel Risk Score to Predict Hungry Bone Syndrome After Parathyroidectomy for Renal Hyperparathyroidism
Ramesh, Sruthi; Vekaria, Shivani; Fisher, Jason C; Wright, Kyla; Underwood, Hunter; Prescott, Jason; Allendorf, John; Patel, Kepal N; Suh, Insoo; Sum, Melissa
OBJECTIVE:Hungry bone syndrome (HBS) is a known complication of parathyroidectomy. Patients with renal hyperparathyroidism are particularly vulnerable to HBS because of their prolonged exposure to electrolyte abnormalities and elevated parathyroid hormone (PTH). However, in-depth characterization of predictive factors for HBS in these patients is lacking. METHODS:A retrospective analysis was performed of patients with renal hyperparathyroidism who underwent parathyroidectomy at a single institution from 2011-2021. Patient demographics, clinical characteristics, and biochemical data were collected and analyzed. Boruta and binary logistic regression analyses were used to develop a scoring system. RESULTS:Thirty-three patients were identified; 16 (48%) developed HBS. Patients with HBS had significantly higher preoperative levels of serum PTH (mean difference [MS] = 2167.2 pg/mL, P <.001), phosphorus (MD = 3.5 mg/dl, P <.001), and alkaline phosphatase (ALP) (MD = 344.2 U/L, P =.002) and significantly lower levels of preoperative serum calcium (MD = -0.96 mg/dL, P =.004). Stepwise regression analysis identified elevated ALP (>150 U/L) and markedly elevated PTH (>1000 pg/mL) as positive predictors of HBS. A two-point scoring system with these 2 variables had overall diagnostic accuracy of 96.8% (sensitivity 100% and specificity 94.1%) with 1 point conferring 93.8% positive predictive value and 2 points conferring 100% positive predictive value. CONCLUSION/CONCLUSIONS:Preoperative serum PTH and ALP are significantly associated with HBS in patients with renal hyperparathyroidism undergoing parathyroidectomy for renal hyperparathyroidism. A scoring system with these 2 variables may be of clinical utility in predicting patients at high risk of HBS.
PMID: 37678470
ISSN: 1530-891x
CID: 5708602
Educational Case: Clinical and pathologic features of primary hyperparathyroidism
Roig, Nicholas J.; Sum, Melissa; Magid, Margret S.
SCOPUS:85147829304
ISSN: 2374-2895
CID: 5425222
Tumor-Induced Osteomalacia Localized and Excised After Pregnancy [Case Report]
Sum, Melissa; Hoda, Syed T; Rapp, Timothy; Zan, Elcin
Objective/UNASSIGNED:Tumor-induced osteomalacia (TIO) is a rare osteomalacia characterized by paraneoplastic secretion of fibroblast growth factor 23. Concomitant occurrence of TIO during pregnancy is rarer still. Our objective was to report a young patient with debilitating fractures diagnosed with TIO who became pregnant and subsequently had her tumor localized by gallium-68 (Ga-68) DOTATATE positron emission tomography/magnetic resonance imaging (PET/MRI). Case Report/UNASSIGNED:A 28 year-old woman with a 2-year history of stress fractures was found to have the following: (1) alkaline phosphatase level, 220 (reference range, 30-95) U/L; (2) phosphorus level, 2.1 (2.5-5.0) mg/dL; (3) 1,25-dihydroxyvitamin D3 level, <8 (18-72) pg/mL; (4) 24-hour urine phosphorus level, 0.5 (0.3-1.3) g; and (5) fibroblast growth factor 23 levels, 1241 (reference range, <180) RU/mL. The patient became pregnant, and at term, a cesarean delivery was performed. Ga-68 DOTATATE PET/MRI showed a 9-mm intracortical mass in the right fibular head and right femoral and bilateral calcaneal stress fractures. The fibular lesion was resected; pathology showed a 1.5-cm lesion with positive fibroblast growth factor receptor 1 staining. Discussion/UNASSIGNED:This patient with TIO had an uneventful pregnancy and delivery. TIO is typically caused by benign mesenchymal tumors. Ga-68 DOTATATE PET/computed tomography has been used for localizing tumors causing TIO, yet MRI has superior contrast resolution over computed tomography. Therefore, it is not surprising that Ga-68 PET/MRI successfully localized this patient's tumor to the intracortical space of the fibular head and distinguished it from insufficiency fractures. Conclusion/UNASSIGNED:To our knowledge, this is the first report of phosphate treatment in a pregnant patient with TIO and the first report of a tumor-inducing TIO being localized by Ga-68 DOTATATE PET/MRI.
PMCID:8573288
PMID: 34765732
ISSN: 2376-0605
CID: 5050752
A Case Report: Euglycemic Diabetic Ketoacidosis Presenting as Chest Pain in a Patient on a Low Carbohydrate Diet [Case Report]
Dorcely, Brenda; Nitis, Juliana; Schwartzbard, Arthur; Newman, Jonathan; Goldberg, Ira; Sum, Melissa
INTRODUCTION/BACKGROUND:Sodium-glucose cotransporter-2 [SGLT2] inhibitors reduce cardiovascular events and mortality in patients with diabetes, particularly patients with established cardiovascular disease. Euglycemic diabetic ketoacidosis [euDKA], a complication of SGLT2 therapy, can be exacerbated by a low carbohydrate diet. CASE REPORT/METHODS:A 61-year-old man with a history of type 2 diabetes, taking a SGLT2 inhibitor empagliflozin 10 mg orally daily, presented to the emergency room with a 2-day history of nausea and chest pain. A week prior to presentation, he had started a ketogenic diet. He was initially admitted with a diagnosis of acute coronary syndrome. On initial assessment in the emergency room, his cardiac enzymes were normal and there were no ischemic changes in his ECG. As there was concern for unstable angina, he underwent cardiac catheterization, which showed a known total occlusion with collaterals and arteries with non-obstructive disease without evidence of acute plaque rupture. His baseline laboratory assessments revealed an elevated anion gap of 17, increased urinary and plasma ketones, and metabolic acidosis. His plasma glucose level was 84 mg/dL. The diagnosis of euDKA was made, and treatment with intravenous fluids and insulin was initiated. His chest pain and nausea subsequently resolved. CONCLUSION/CONCLUSIONS:We present a case of euDKA triggered by a ketogenic diet while on SGLT2 inhibitor therapy presenting as chest pain. The recognition of euDKA is important in the context of increased SGLT2 use for management of cardiovascular risk for patients with diabetes.
PMID: 32178617
ISSN: 1875-6417
CID: 4353492
Functional Magnetic Resonance Imaging in Primary Hyperparathyroidism
Gazes, Yunglin; Liu, Minghao; Sum, Melissa; Cong, Elaine; Kuo, Jennifer; Lee, James A; Silverberg, Shonni; Stern, Yaakov; Walker, Marcella
OBJECTIVE:The neurophysiological mechanisms underlying cognitive dysfunction in primary hyperparathyroidism (PHPT) and brain regions affected are not clear. We assessed neural activation during cognitive testing (matrix reasoning, paired associates, and logical memory) using functional magnetic resonance imaging (fMRI) in 23 patients with PHPT and 23 healthy controls. A subset with PHPT was re-assessed 6 months post- parathyroidectomy (PTX). DESIGN/METHODS:This is an observational study comparing neural activation by fMRI in patients with PHPT to normative controls. Postmenopausal women were studied at a tertiary referral center. RESULTS:There were no between-group differences in cognitive task performance. Patients with PHPT had lower neural activation versus controls (max Z = 4.02, all p<0.01) during matrix reasoning in brain regions involved in executive function [left frontal lobe (k=57) and right medial frontal gyrus (k=72)] and motor function [right precentral gyrus (k=51)]. During paired associates (verbal memory), those with PHPT had greater activation in the right inferior parietal lobule (language/mathematical operations; k=65, p<0.01). Greater activation in this region bilaterally correlated with higher PTH (k=96, p<0.01). Post-PTX, activation decreased during matrix reasoning, but in different regions than those affected pre-PTX. CONCLUSIONS:PHPT is associated with differences in task-related neural activation patterns, but no difference in cognitive performance. While this may indicate compensation to maintain the same cognitive function, there was no clear improvement in neural activation after PTX. Larger, longitudinal studies that include PHPT patients followed without surgery are needed to determine if PTX could prevent worsening of altered neural activation patterns in PHPT.
PMID: 32348956
ISSN: 1479-683x
CID: 4436942
ATRAID regulates the action of nitrogen-containing bisphosphonates on bone
Surface, Lauren E; Burrow, Damon T; Li, Jinmei; Park, Jiwoong; Kumar, Sandeep; Lyu, Cheng; Song, Niki; Yu, Zhou; Rajagopal, Abbhirami; Bae, Yangjin; Lee, Brendan H; Mumm, Steven; Gu, Charles C; Baker, Jonathan C; Mohseni, Mahshid; Sum, Melissa; Huskey, Margaret; Duan, Shenghui; Bijanki, Vinieth N; Civitelli, Roberto; Gardner, Michael J; McAndrew, Chris M; Ricci, William M; Gurnett, Christina A; Diemer, Kathryn; Wan, Fei; Costantino, Christina L; Shannon, Kristen M; Raje, Noopur; Dodson, Thomas B; Haber, Daniel A; Carette, Jan E; Varadarajan, Malini; Brummelkamp, Thijn R; Birsoy, Kivanc; Sabatini, David M; Haller, Gabe; Peterson, Timothy R
Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, are the most widely prescribed medications for diseases involving bone, with nearly 200 million prescriptions written annually. Recently, widespread use of N-BPs has been challenged due to the risk of rare but traumatic side effects such as atypical femoral fracture (AFF) and osteonecrosis of the jaw (ONJ). N-BPs bind to and inhibit farnesyl diphosphate synthase, resulting in defects in protein prenylation. Yet, it remains poorly understood what other cellular factors might allow N-BPs to exert their pharmacological effects. Here, we performed genome-wide studies in cells and patients to identify the poorly characterized gene, ATRAID Loss of ATRAID function results in selective resistance to N-BP-mediated loss of cell viability and the prevention of alendronate-mediated inhibition of prenylation. ATRAID is required for alendronate inhibition of osteoclast function, and ATRAID-deficient mice have impaired therapeutic responses to alendronate in both postmenopausal and senile (old age) osteoporosis models. Last, we performed exome sequencing on patients taking N-BPs that suffered ONJ or an AFF. ATRAID is one of three genes that contain rare nonsynonymous coding variants in patients with ONJ or an AFF that is also differentially expressed in poor outcome groups of patients treated with N-BPs. We functionally validated this patient variation in ATRAID as conferring cellular hypersensitivity to N-BPs. Our work adds key insight into the mechanistic action of N-BPs and the processes that might underlie differential responsiveness to N-BPs in people.
PMID: 32434850
ISSN: 1946-6242
CID: 4446942
Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy
Liu, M; Sum, M; Cong, E; Colon, I; Bucovsky, M; Williams, J; Kepley, A; Kuo, J; Lee, J A; Lazar, R M; Marshall, R; Silverberg, S; Walker, M D
PURPOSE/OBJECTIVE:There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS:This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS:Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS:Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.
PMID: 31621051
ISSN: 1720-8386
CID: 4140572
Acute hypocalcemia from proton pump inhibitor use
Chapter by: Vallejo, Franco; Sum, Melissa
in: Hypoparathyroidism: A Clinical Casebook by
[S.l.] : Springer International Publishing, 2019
pp. 9-15
ISBN: 9783030294328
CID: 4543732
Incidental thyroid carcinoma in graves'disease-should we be concerned? [Meeting Abstract]
Ho, E; Cheng, Y; Liu, C; Sum, M; Ogilvie, J; Givi, B; Patel, K
The incidence of thyroid cancer in Graves'Disease (GD) patients is estimated to be low. However, it is unclear what impact the recent rise in the incidence of thyroid cancers has had in this population. Furthermore, it is not clear if these cancers behave more aggressively than cancers in the general population. We investigated the incidence of malignancy and its features in a contemporary cohort of GD patients treated by surgery. All patients who underwent thyroidectomy for GD in our center were reviewed from 2013-2018. Demographics, clinicopathologic features, rate of incidental cancer and outcomes were reviewed. We identified 130 patients with GD who underwent thyroidectomy. Median age was 40.5 (16-80). Majority were female (112, 86%). All but five (4%) were radioactive iodine naive. Thirtyfour (26%) were found to harbor malignancy. While the majority (18, 53%) were papillary microcarcinoma; 12 (34%) had multifocal disease; 10 (29%) had tall cell features, 3 (9%) had positive lymph nodes, and 2 (6%) had extrathyroidal extension. One patient (3%) was diagnosed with follicular carcinoma. No permanent hyperparathyroidism or recurrent laryngeal nerve injury was encountered. With a median follow up of 23 months no recurrences were identified. The risk of incidental malignancy in GD patients was high in our cohort. While the majority were low risk microcarcinomas, a number of patients harbored higher risk tall cell features. Our data suggest that for GD patients who are medically managed, careful surveillance and biopsy of suspicious nodules might be warranted. The outcome of surgical treatment was excellent for controlling both hyperthyroidism and cancer
EMBASE:629777461
ISSN: 1557-9077
CID: 4187912
Clinical and Diffusion Tensor MRI Findings in Congenital Homonymous Hemianopia
Rispoli, Joanne; Seay, Meagan; Sum, Melissa; Rucker, Janet C; Shepherd, Timothy M
PMID: 30865055
ISSN: 1536-5166
CID: 3733222