Search Results
Search for other papers by Qian Wang in
Google Scholar
PubMed
Search for other papers by Jiacheng Wang in
Google Scholar
PubMed
Search for other papers by Yunhui Xin in
Google Scholar
PubMed
Search for other papers by Ziyang He in
Google Scholar
PubMed
Search for other papers by Xiang Zhou in
Google Scholar
PubMed
Search for other papers by Xing Liu in
Google Scholar
PubMed
Search for other papers by Teng Zhao in
Google Scholar
PubMed
Search for other papers by Lihan He in
Google Scholar
PubMed
Search for other papers by Hong Shen in
Google Scholar
PubMed
Search for other papers by Mulan Jin in
Google Scholar
PubMed
Search for other papers by Bojun Wei in
Google Scholar
PubMed
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.
Search for other papers by Kelly Brewer in
Google Scholar
PubMed
Search for other papers by Isabel Nip in
Google Scholar
PubMed
Search for other papers by Justin Bellizzi in
Google Scholar
PubMed
Center for Regenerative Medicine and Skeletal Development, Department of Reconstructive Sciences, University of Connecticut School of Dental Medicine, Farmington, Connecticut, USA
Search for other papers by Jessica Costa-Guda in
Google Scholar
PubMed
Division of Endocrinology and Metabolism, University of Connecticut School of Medicine, Farmington, Connecticut, USA
Search for other papers by Andrew Arnold in
Google Scholar
PubMed
Objective
Primary hyperparathyroidism is most often caused by a sporadic single-gland parathyroid adenoma (PTA), a tumor type for which cyclin D1 is the only known and experimentally validated oncoprotein. However, the molecular origins of its frequent overexpression have remained mostly elusive. In this study, we explored a potential tumorigenic mechanism that could increase cyclin D1 stability through a defect in molecules responsible for its degradation.
Methods
We examined two tumor suppressor genes known to modulate cyclin D1 ubiquitination, PRKN and FBXO4 (FBX4), for evidence of classic two-hit tumor suppressor inactivation within a cohort of 82 PTA cases. We examined the cohort for intragenic inactivating and splice site mutations by Sanger sequencing and for locus-associated loss of heterozygosity (LOH) by microsatellite analysis.
Results
We identified no evidence of bi-allelic tumor suppressor inactivation of PRKN or FBXO4 via inactivating mutation or splice site perturbation, neither in combination with nor independent of LOH. Among the 82 cases, we encountered previously documented benign single nucleotide polymorphisms (SNPs) in 35 tumors at frequencies similar to those reported in the germlines of the general population. Eight cases exhibited intragenic LOH at the PRKN locus, in some cases extending to cover at least an additional 1.7 Mb of chromosome 6q25-26. FBXO4 was not affected by LOH.
Conclusion:
The absence of evidence for specific bi-allelic inactivation in PRKN and FBXO4 in this sizeable cohort suggests that these genes only rarely, if ever, serve as classic driver tumor suppressors responsible for the growth of PTAs.
Search for other papers by Xiao-Ping Qi in
Google Scholar
PubMed
Search for other papers by Jian-Zhong Peng in
Google Scholar
PubMed
Search for other papers by Xiao-Wei Yang in
Google Scholar
PubMed
Search for other papers by Zhi-Lie Cao in
Google Scholar
PubMed
Search for other papers by Xiu-Hua Yu in
Google Scholar
PubMed
Search for other papers by Xu-Dong Fang in
Google Scholar
PubMed
Search for other papers by Da-Hong Zhang in
Google Scholar
PubMed
Search for other papers by Jian-Qiang Zhao in
Google Scholar
PubMed
Background
Cutaneous lichen amyloidosis (CLA) has been reported in some multiple endocrine neoplasia type 2A (MEN 2A) families affected by specific germline RET mutations C634F/G/R/W/Y or V804M, as a characteristic of the clinical manifestation in ‘MEN 2A with CLA’, one of four variants of MEN 2A, which was strictly located in the scapular region of the upper back.
Patient Findings
This study reports a large south-eastern Chinese pedigree with 17 individuals carrying the MEN 2A-harboring germline C611Y (c.1832G>A) RET mutation by Sanger sequencing. One individual presented MEN 2A-related clinical features, including typical CLA in the interscapular region; another individual exhibited neurological pruritus and scratching in the upper back but lacked CLA skin lesions. Both subjects presented with CLA or pruritic symptoms several years before the onset of medullary thyroid carcinoma (MTC) and/or pheochromocytoma. The remaining 15 RET mutation carriers did not exhibit CLA; of these, one presented with MTC and pheochromocytoma, nine with MTC only, two with elevated serum calcitonin and three younger subjects with normal serum calcitonin levels. This family’s clinical data revealed a later diagnosis of MTC (mean age, 45.9 (range: 23–73) years), a lower penetrance of pheochromocytoma (2/17, 11.8%) and CLA (1/17, 5.9%). However, no hyperparathyroidism and Hirschsprung disease were reported in this family.
Summary and Conclusions
This is the first description of a family with MEN 2A-related CLA due to a germline RET C611Y mutation, which might exhibit a novel and diversified genotype–phenotype spectrum in MEN 2A.
Search for other papers by Elizaveta Mamedova in
Google Scholar
PubMed
Search for other papers by Natalya Mokrysheva in
Google Scholar
PubMed
Search for other papers by Evgeny Vasilyev in
Google Scholar
PubMed
Search for other papers by Vasily Petrov in
Google Scholar
PubMed
Search for other papers by Ekaterina Pigarova in
Google Scholar
PubMed
Search for other papers by Sergey Kuznetsov in
Google Scholar
PubMed
Search for other papers by Nikolay Kuznetsov in
Google Scholar
PubMed
Search for other papers by Liudmila Rozhinskaya in
Google Scholar
PubMed
Institute of Clinical Endocrinology, Endocrinology Research Center, Moscow, Russian Federation
Search for other papers by Galina Melnichenko in
Google Scholar
PubMed
Search for other papers by Ivan Dedov in
Google Scholar
PubMed
Search for other papers by Anatoly Tiulpakov in
Google Scholar
PubMed
Background
Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.
Objective
To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.
Design
We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had MEN1 mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.
Methods
The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (MEN1, CASR, CDC73, CDKN1A, CDKN1B, CDKN1C, CDKN2A, CDKN2C, CDKN2D). In cases suspicious for gross CDC73 deletions multiplex ligation-dependent probe amplification was performed.
Results
NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in CDC73 c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in CASR c.3145G>T (p.Glu1049*) and one in MEN1 c.784-9G>A. In two patients, MLPA confirmed gross CDC73 deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom CDC73 mutations were found in 5/8.
Conclusions
Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with CDC73 mutations.
Search for other papers by Elena Pardi in
Google Scholar
PubMed
Search for other papers by Stefano Mariotti in
Google Scholar
PubMed
Search for other papers by Natalia S Pellegata in
Google Scholar
PubMed
Search for other papers by Katiuscia Benfini in
Google Scholar
PubMed
Search for other papers by Simona Borsari in
Google Scholar
PubMed
Search for other papers by Federica Saponaro in
Google Scholar
PubMed
Search for other papers by Liborio Torregrossa in
Google Scholar
PubMed
Search for other papers by Antonello Cappai in
Google Scholar
PubMed
Search for other papers by Chiara Satta in
Google Scholar
PubMed
Search for other papers by Marco Mastinu in
Google Scholar
PubMed
Search for other papers by Claudio Marcocci in
Google Scholar
PubMed
Search for other papers by Filomena Cetani in
Google Scholar
PubMed
Inactivating germline mutations of the CDKN1B gene encoding the nuclear cyclin-dependent kinase inhibitor P27kip1 protein have been reported in patients with multiple endocrine neoplasia type 4 (MEN4), a MEN1-like phenotype without MEN1 mutations. The aim of this study was to characterize in vitro the germline CDKN1B mutation c.374_375delCT (S125X) we detected in a patient with MEN4. The proband was affected by primary hyperparathyroidism due to multiglandular parathyroid involvement and gastro–entero–pancreatic tumors. We carried out subcellular localization experiments by transfection with plasmid vectors expressing the WT or mutant CDKN1B cDNA into the eukaryotic human cervix adenocarcinoma (HeLa) and GH3 cell lines. Results from western blotting studies indicated that fusion proteins were expressed at equal levels. The mutated protein was shorter compared with the WT protein and lacked the highly conserved C-terminal domain, which includes the bipartite nuclear localization signal at amino acids 152/153 and 166/168. In HeLa and GH3 cells, WT P27 localized in the nucleus, whereas the P27_S125X protein was retained in the cytoplasm, predicting the loss of tumor-suppressive function. The proband's tumoral parathyroid tissue did not show allelic loss, because both WT and mutant alleles were determined to be present by sequencing the somatic DNA. Immunohistochemistry revealed a complete loss of nuclear expression of P27 in a parathyroid adenoma, which had been removed by the second surgery in the patient. In conclusion, our results confirm the pathogenic role of the c.374_375delCT CDKN1B germline mutation in a patient with MEN4.
Search for other papers by Luchuan Li in
Google Scholar
PubMed
Search for other papers by Baoyuan Li in
Google Scholar
PubMed
Search for other papers by Bin Lv in
Google Scholar
PubMed
Search for other papers by Weili Liang in
Google Scholar
PubMed
Search for other papers by Binbin Zhang in
Google Scholar
PubMed
Search for other papers by Qingdong Zeng in
Google Scholar
PubMed
Search for other papers by Andrew G Turner in
Google Scholar
PubMed
Search for other papers by Lei Sheng in
Google Scholar
PubMed
Background
Multiple studies have reported the increased incidence of thyroid cancer in patients with primary hyperparathyroidism (PHPT). However, the underlying risk factors of concomitant thyroid cancer in patients with PHPT remain unknown. The primary aim of this study was to examine the records of patients with PHPT to identify characteristics that correlated with the presence of coexisting thyroid nodules, and which may have an implication for the prediction of thyroid cancer.
Methods
Medical records of consecutive patients with PHPT (n = 318) were reviewed from January 2010 to September 2020 in two tertiary medical centers in China. Patient clinicopathological and biological data were collected and analyzed.
Results
Of a total of 318 patients with PHPT, 105 (33.0%) patients had thyroid nodules and 26 (8.2%) patients were concomitant with thyroid cancer. A total of 38 thyroid nodules taken from 26 patients were pathologically assessed to be well-differentiated papillary thyroid carcinoma (PTC), with 81% being papillary thyroid microcarcinoma (PTMC). In 79% (30/38) of these cancers, thyroid nodules were considered suspicious following preoperative ultrasound. Multinomial logistic regression analysis revealed that female gender was associated with increased risk of thyroid nodules (OR = 2.13, 95% CI: 1.13–3.99, P = 0.019), while lower log-transformed parathyroid hormone levels were an independent predictor of thyroid cancer in patients with PHPT (OR = 0.50, 95% CI: 0.26–0.93, P = 0.028).
Conclusion
In conclusion, we observed a relatively high prevalence of thyroid cancer in our cohort of Chinese patients with PHPT. Evaluation of thyroid nodules by preoperative ultrasound may be advisable in patients with PHPT, particularly for females and patients with modestly elevated serum parathyroid hormone levels.
Search for other papers by Louise Vølund Larsen in
Google Scholar
PubMed
Search for other papers by Delphine Mirebeau-Prunier in
Google Scholar
PubMed
Search for other papers by Tsuneo Imai in
Google Scholar
PubMed
Search for other papers by Cristina Alvarez-Escola in
Google Scholar
PubMed
Search for other papers by Kornelia Hasse-Lazar in
Google Scholar
PubMed
Search for other papers by Simona Censi in
Google Scholar
PubMed
Search for other papers by Luciana A Castroneves in
Google Scholar
PubMed
Search for other papers by Akihiro Sakurai in
Google Scholar
PubMed
Search for other papers by Minoru Kihara in
Google Scholar
PubMed
Search for other papers by Kiyomi Horiuchi in
Google Scholar
PubMed
Réseau TenGen, Marseille, France
Search for other papers by Véronique Dorine Barbu in
Google Scholar
PubMed
Fédération d’Endocrinologie, Hospices Civils de Lyon, Université Lyon 1, France
Search for other papers by Francoise Borson-Chazot in
Google Scholar
PubMed
Service de Génétique, AP-HP, Hôpital européen Georges Pompidou, Paris, France
Université de Paris, PARCC, INSERM, Paris, France
Search for other papers by Anne-Paule Gimenez-Roqueplo in
Google Scholar
PubMed
Laboratoire de Biochimie et Oncologie Moléculaire, CHU Lille, Lille, France
Search for other papers by Pascal Pigny in
Google Scholar
PubMed
Laboratoire de Génétique Moléculaire, CHU Lyon, Lyon, France
Search for other papers by Stephane Pinson in
Google Scholar
PubMed
Search for other papers by Nelson Wohllk in
Google Scholar
PubMed
Search for other papers by Charis Eng in
Google Scholar
PubMed
Search for other papers by Berna Imge Aydogan in
Google Scholar
PubMed
Search for other papers by Dhananjaya Saranath in
Google Scholar
PubMed
Search for other papers by Sarka Dvorakova in
Google Scholar
PubMed
Department of Endocrinology, Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital de la Conception, Centre de Référence des Maladies Rares de l’hypophyse HYPO, Marseille, France
Search for other papers by Frederic Castinetti in
Google Scholar
PubMed
Search for other papers by Attila Patocs in
Google Scholar
PubMed
Search for other papers by Damijan Bergant in
Google Scholar
PubMed
Search for other papers by Thera P Links in
Google Scholar
PubMed
Search for other papers by Mariola Peczkowska in
Google Scholar
PubMed
Search for other papers by Ana O Hoff in
Google Scholar
PubMed
Search for other papers by Caterina Mian in
Google Scholar
PubMed
Search for other papers by Trisha Dwight in
Google Scholar
PubMed
Search for other papers by Barbara Jarzab in
Google Scholar
PubMed
Search for other papers by Hartmut P H Neumann in
Google Scholar
PubMed
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain
Search for other papers by Mercedes Robledo in
Google Scholar
PubMed
Search for other papers by Shinya Uchino in
Google Scholar
PubMed
Aix Marseille Univ, APHM, INSERM, MMG, Laboratory of Molecular Biology, Hospital La Conception, Marseille, France
Search for other papers by Anne Barlier in
Google Scholar
PubMed
Search for other papers by Christian Godballe in
Google Scholar
PubMed
Department of Clinical Research, University of Southern Denmark, Odense, Denmark
Search for other papers by Jes Sloth Mathiesen in
Google Scholar
PubMed
Objective
Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.
Design and methods
An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017.
Results
Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.
Conclusions
Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.
Search for other papers by Magdaléna Fořtová in
Google Scholar
PubMed
Search for other papers by Lenka Hanousková in
Google Scholar
PubMed
Search for other papers by Martin Valkus in
Google Scholar
PubMed
Search for other papers by Jana Čepová in
Google Scholar
PubMed
Search for other papers by Richard Průša in
Google Scholar
PubMed
Search for other papers by Karel Kotaška in
Google Scholar
PubMed
Background
Fibroblast growth factor 23 (FGF23) is a key regulator of urine phosphate excretion. The aim of the study was to investigate the perioperative (intraoperative and postoperative) changes of plasma intact and C-terminal FGF23 (iFGF23, cFGF23) concentrations in patients with primary hyperparathyroidism (pHPT) submitted to surgery.
Materials and methods
The study involved 38 adult patients with pHPT caused by adenoma. Parathyroid hormone (PTH) levels were investigated intraoperatively (just before the incision and 10 min after adenoma excision). cFGF23, iFGF23, phosphate, estimated glomerular filtration rate (eGFR), and procollagen type 1 N-terminal propetide (P1NP) were measured intraoperatively and postoperatively (next day after the surgery).
Results
PTH levels decreased intraoperatively (13.10 pmol/L vs 4.17 pmol/L, P< 0.0001). FGF23 levels measured intraoperatively were at the upper level of reference interval. cFGF23 decreased postoperatively compared with the values measured just before the incision (cFGF23: 89.17 RU/mL vs 22.23 RU/mL, P< 0.0001). iFGF23 decreased as well, but the postoperative values were low. Postoperative inorganic phosphate values increased (1.03 mmol/L vs 0.8 mmol/L, P= 0.0025). We proved significant negative correlation of perioperative FGF23 with inorganic phosphate (cFGF23: Spearman’s r = −0.253, P= 0.0065; iFGF23: Spearman’s r = −0.245, P= 0.0085). We also found that FGF23 values just before incision correlated with eGFR (cystatin C) (cFGF23: Spearman’s r = −0.499, P= 0.0014; iFGF23: Spearman’s r = −0.413, P= 0.01).
Conclusion
Intraoperative iFGF23 and cFGF23 did not change despite PTH decreased significantly. cFGF23 and iFGF23 significantly decreased 1 day after parathyroidectomy and are associated with increase of inorganic phosphate in pHPT patients. cFGF23 and iFGF23 just before incision correlated with eGFR (cystatin C). Similar results found in both iFGF23 and cFGF23 suggest that each could substitute the other.
Search for other papers by Hélène Singeisen in
Google Scholar
PubMed
Search for other papers by Mariko Melanie Renzulli in
Google Scholar
PubMed
Search for other papers by Vojtech Pavlicek in
Google Scholar
PubMed
Search for other papers by Pascal Probst in
Google Scholar
PubMed
Search for other papers by Fabian Hauswirth in
Google Scholar
PubMed
Search for other papers by Markus K Muller in
Google Scholar
PubMed
Search for other papers by Magdalene Adamczyk in
Google Scholar
PubMed
Search for other papers by Achim Weber in
Google Scholar
PubMed
Search for other papers by Reto Martin Kaderli in
Google Scholar
PubMed
Search for other papers by Pietro Renzulli in
Google Scholar
PubMed
Objective
Multiple endocrine neoplasia type 4 (MEN4) is caused by a CDKN1B germline mutation first described in 2006. Its estimated prevalence is less than one per million. The aim of this study was to define the disease characteristics.
Methods
A systematic review was performed according to the PRISMA 2020 criteria. A literature search from January 2006 to August 2022 was done using MEDLINE® and Web of ScienceTM.
Results
Forty-eight symptomatic patients fulfilled the pre-defined eligibility criteria. Twenty-eight different CDKN1B variants, mostly missense (21/48, 44%) and frameshift mutations (17/48, 35%), were reported. The majority of patients were women (36/48, 75%). Men became symptomatic at a median age of 32.5 years (range 10–68, mean 33.7 ± 23), whereas the same event was recorded for women at a median age of 49.5 years (range 5–76, mean 44.8 ± 19.9) (P = 0.25). The most frequently affected endocrine organ was the parathyroid gland (36/48, 75%; uniglandular disease 31/36, 86%), followed by the pituitary gland (21/48, 44%; hormone-secreting 16/21, 76%), the endocrine pancreas (7/48, 15%), and the thyroid gland (4/48, 8%). Tumors of the adrenal glands and thymus were found in three and two patients, respectively. The presenting first endocrine pathology concerned the parathyroid (27/48, 56%) and the pituitary gland (11/48, 23%). There were one (27/48, 56%), two (13/48, 27%), three (3/48, 6%), or four (5/48, 10%) syn- or metachronously affected endocrine organs in a single patient, respectively.
Conclusion
MEN4 is an extremely rare disease, which most frequently affects women around 50 years of age. Primary hyperparathyroidism as a uniglandular disease is the leading pathology.
Search for other papers by Maria Angela D'amico in
Google Scholar
PubMed
Search for other papers by Barbara Ghinassi in
Google Scholar
PubMed
Search for other papers by Pascal Izzicupo in
Google Scholar
PubMed
Search for other papers by Lamberto Manzoli in
Google Scholar
PubMed
Search for other papers by A Di Baldassarre in
Google Scholar
PubMed
Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.
