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Marília D’Elboux Guimarães Brescia Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil
Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Karine Candido Rodrigues Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil
Endocrine Oncology Division, Institute of Cancer of the State of São Paulo (ICESP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, São Paulo, Brazil

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André Fernandes d’Alessandro Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Wellington Alves Filho Department of Surgery, Walter Cantidio University Hospital, Federal University of Ceara School of Medicine (FAMED-UFC), Fortaleza, Brazil

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Willemijn Y van der Plas Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Schelto Kruijff Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Sergio Samir Arap Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Sergio Pereira de Almeida Toledo Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil

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Fábio Luiz de Menezes Montenegro Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Delmar Muniz Lourenço Jr Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil
Endocrine Oncology Division, Institute of Cancer of the State of São Paulo (ICESP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, São Paulo, Brazil

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Background

Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown.

Method

Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume.

Results

Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = −0.60, P = 0.0004) and MCS (r = −0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities.

Conclusion

A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.

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Qian Wang Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Jiacheng Wang Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Yunhui Xin Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Ziyang He Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Xiang Zhou Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Xing Liu Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Teng Zhao Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Lihan He Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Hong Shen Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Mulan Jin Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Bojun Wei Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Background

Parathyroid carcinoma (PC), often misdiagnosed as a parathyroid adenoma (PA), is prone to local relapse due to the initial surgery being restricted to parathyroid lesions instead of en bloc resection of parathyroid lesions with negative incision margins. However, it is very challenging to distinguish PC from PA preoperatively; hence, this study investigated an effective biomarker for increasing accuracy in PC diagnosis.

Method

First, the differentially expressed circular RNAs between three PC tissues and three PA tissues were screened by high-throughput circular RNA sequencing, and the expression of hsa_circ_0005729 was verified by qRT-PCR in 14 patients with PC and 40 patients with PA. Secondly, the receiver operating characteristic curve and the area under the curve (AUC) were used to analyze the diagnostic efficiency of hsa_circ_0005729 in PC by combining with laboratory data. Thirdly, RNF138mRNA, the corresponding linear transcript of hsa_circ_0005729, was measured, and the relationship between hsa_circ_0005729 and RNF138 mRNA was analyzed in patients with PA and patients with PC.

Results

Hsa_circ_0005729 expression was significantly higher in patients with PC than in patients with PA. Serum calcium (P  = 0.045), alkaline phosphatase (ALP) (P  = 0.048), and creatinine levels (P  = 0.036) were significantly higher in patients with PC than in patients with PA. The AUC increased to 0.86 when hsa_circ_0005729 combined with serum calcium, creatinine, and ALP. In addition, hsa_circ_0005729 was positively correlated with RNF138 mRNA in patients with PA but not in patients with PC.

Conclusion

The novel circular RNA hsa_circ_0005729 was found to have a higher expression in patients with PC, indicating its usefulness for distinguishing PC from PA.

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Heng Yeh Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
College of Medicine, Chang Gung University, Taoyuan, Taiwan

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Hsuan Yeh College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Chun-Cheng Chiang College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Ju-Ching Yen College of Medicine, China Medical University, Taichung, Taiwan

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I-Kuan Wang College of Medicine, China Medical University, Taichung, Taiwan
Department of Nephrology, China Medical University Hospital, Taichung, Taiwan

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Shou-Hsuan Liu College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Cheng-Chia Lee College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Cheng-Hao Weng College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Wen-Hung Huang College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Ching-Wei Hsu College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Tzung-Hai Yen College of Medicine, Chang Gung University, Taoyuan, Taiwan
Department of Nephrology, Clinical Poison Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan

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Secondary hyperparathyroidism (SHPT) is a common complication of end-stage kidney disease (ESKD). Hungry bone syndrome (HBS) occurs frequently in patients on maintenance dialysis receiving parathyroidectomy for refractory SHPT. However, there is scanty study investigating the clinical risk factors that predict postoperative HBS, and its outcome in peritoneal dialysis (PD) patients. We conducted a single-center retrospective study to analyze 66 PD patients who had undergone parathyroidectomy for secondary hyperparathyroidism at Chang Gung Memorial Hospital between 2009 and 2019. The patients were stratified into two groups based on the presence (n=47) or absence (n=19) of HBS after parathyroidectomy. Subtotal parathyroidectomy was the most common surgery performed (74.2%), followed by total parathyroidectomy with autoimplantation (25.8%). Pathological examination of all surgical specimens revealed parathyroid hyperplasia (100%). Patients with HBS had lower levels of postoperative nadir corrected calcium, higher alkaline phosphate (ALP), and higher potassium levels compared with patients without HBS (all P<0.05). A multivariate logistic regression model confirmed that lower preoperative serum calcium level (OR 0.354, 95% CI 0.133–0.940, P=0.037), higher ALP (OR 1.026, 95% CI 1.008–1.044, P=0.004), and higher potassium level (OR 6.894, 95% CI 1.806–26.317, P=0.005) were associated with HBS after parathyroidectomy. Patients were followed for 58.2±30.8 months after the surgery. There was no significant difference between HBS and non-HBS groups in persistence (P=0.496) or recurrence (P=1.000) of hyperparathyroidism. The overall mortality rate was 10.6% with no significant difference found between both groups (P=0.099). We concluded that HBS is a common complication (71.2%) of parathyroidectomy for SHPT and should be managed appropriately.

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Sara Lomelino Pinheiro Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Ana Saramago Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Branca Maria Cavaco Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Carmo Martins Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Valeriano Leite Serviço de Endocrinologia e Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Tiago Nunes da Silva Serviço de Endocrinologia e Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4–10.2) and 472 pg/mL (12–65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

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Keiko Ohkuwa Department of Surgery, Ito Hospital, Tokyo, Japan

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Kiminori Sugino Department of Surgery, Ito Hospital, Tokyo, Japan

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Ryohei Katoh Department of Pathology, Ito Hospital, Tokyo, Japan

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Mitsuji Nagahama Department of Surgery, Ito Hospital, Tokyo, Japan

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Wataru Kitagawa Department of Surgery, Ito Hospital, Tokyo, Japan

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Kenichi Matsuzu Department of Surgery, Ito Hospital, Tokyo, Japan

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Akifumi Suzuki Department of Surgery, Ito Hospital, Tokyo, Japan

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Chisato Tomoda Department of Surgery, Ito Hospital, Tokyo, Japan

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Kiyomi Hames Department of Surgery, Ito Hospital, Tokyo, Japan

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Junko Akaishi Department of Surgery, Ito Hospital, Tokyo, Japan

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Chie Masaki Department of Surgery, Ito Hospital, Tokyo, Japan

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Kana Yoshioka Department of Surgery, Ito Hospital, Tokyo, Japan

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Koichi Ito Department of Surgery, Ito Hospital, Tokyo, Japan

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Objective

Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism.

Design

This was a retrospective study.

Methods

Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed.

Results

Preoperative intact-parathyroid hormone (P  = 0.0003), serum calcium (P  = 0.0048), and tumor diameter (P  = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P  = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased.

Conclusion

In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.

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