Interference With VIP to Distinguish Between Real and False VIPoma: National Study From the French Endocrine Tumors Group.

Background: Vasoactive intestinal peptide (VIP)-secreting tumors (VIPomas) are digestive neuroendocrine tumors in which the hormonal secretion is life-threatening. Biological confirmation is obtained by demonstrating an elevation in plasma VIP, usually using radioimmunoassay (RIA). In some cases, analytical interference is suspected. We developed 3 different techniques to detect interference in VIP RIA. Methods: Three techniques were used: RIA after Sephadex column chromatography separation, RIA after polyethylene glycol precipitation, and 125I-labeled VIP binding test. We included patients with suspicion of false positive VIP (FPV) elevation. We then compared results with those of a group of "real," proven VIPoma (RV). Results: A total of 15 patients with FPV elevation and 9 RV patients were included. Interference was detected in all FPV patients vs none in RV. Clinical and biochemical parameters did not differ between FPV and RV patients, but VIP concentration in RIA was significantly higher in FPV patients than in RV patients (228 pmol/L vs 66 pmol/L, P = .038). Using a 125I-labeled VIP binding test, median proportion of radioactivity in the pellet was significantly higher in FPV than in RV patients (53% vs 13%, P < .0001). A 20.5% threshold presented excellent performances (sensitivity 100% [79.6-100], specificity 100% [70.1-100]). Conclusion: We developed 3 different laboratory techniques to reveal interference in RIA VIP assays. The diagnostic performance of all 3 was excellent. These techniques must be employed in cases of discordance between VIP elevation and clinical presentation.

Lipomatoses.

Lipomatoses are benign proliferation of adipose tissue. Lipomas (benign fat tumors) are the most common component of lipomatosis. They may be unique or multiple, encapsulated or not, subcutaneous or sometimes visceral. In some cases, they form large areas of non-encapsulated fat hypertrophy, with a variable degree of fibrosis. They can develop despite the absence of obesity. They may be familial or acquired. At difference with lipodystrophy syndromes, they are not associated with lipoatrophy areas, except in some rare cases such as type 2 familial partial lipodystrophy syndromes (FPLD2). Their metabolic impact is variable in part depending on associated obesity. They may have functional or aesthetic consequences. Lipomatosis may be isolated, be part of a syndrome, or may be visceral. Isolated lipomatoses include multiple symmetrical lipomatosis (Madelung disease or Launois-Bensaude syndrome), familial multiple lipomatosis, the painful Dercum's disease also called Adiposis Dolorosa or Ander syndrome, mesosomatic lipomatosis also called Roch-Leri lipomatosis, familial angiolipomatosis, lipedema and hibernomas. Syndromic lipomatoses include PIK3CA-related disorders, Cowden/PTEN hamartomas-tumor syndrome, some lipodystrophy syndromes, and mitochondrial diseases, especially MERRF, multiple endocrine neoplasia type 1, neurofibromatosis type 1, Wilson disease, Pai or Haberland syndromes. Finally, visceral lipomatoses have been reported in numerous organs and sites: pancreatic, adrenal, abdominal, epidural, mediastinal, epicardial… The aim of this review is to present the main types of lipomatosis and their physiopathological component, when it is known.

Beyond MEN1, when to think about MEN4? Retrospective study on 5600 patients in the French population & literature review.

CONTEXT: Germline CDKN1B variants predispose patients to multiple endocrine neoplasia type 4 (MEN4), a rare MEN1-like syndrome, with <100 reported cases since its discovery in 2006. Although CDKN1B mutations are frequently suggested to explain cases of genetically-negative MEN1, the prevalence and phenotype of MEN4 patients is poorly known, and genetic counseling is unclear. OBJECTIVE: To evaluate the prevalence of MEN4 in MEN1-suspected patients and characterize the phenotype of MEN4 patients. DESIGN: Retrospective observational nationwide study. Narrative review of literature and variant class reassessment. PATIENTS: We included all adult patients with class 3/4/5 CDKN1B variants identified by the laboratories from the French TENGEN network between 2015 and 2022 through germline genetic testing for MEN1 suspicion. After class reassessment, we compared the phenotype of symptomatic patients with class 4/5 CDKN1B variants, i.e. with genetically-confirmed MEN4 diagnosis, in our series and in literature with 66 matched MEN1 patients from the UMD-MEN1 database. RESULTS: From 5600 MEN1-suspected patients analyzed, four patients with class 4/5 CDKN1B variant were found (0.07%). They presented with multiple duodenal NET, PHPT and adrenal nodule, isolated PHPT, PHPT and pNET. We listed 29 patients with CDKN1B class 4/5 variants from literature. Compared to matched MEN1 patients, MEN4 patients presented lower NET incidence and older age at PHPT diagnosis. CONCLUSION: The prevalence of MEN4 is low. PHPT and PA represent the main associated lesions, NETs are rare. Our results suggest a milder and later phenotype than in MEN1. Our observations will help to improve genetic counseling and management of MEN4 families.

Proteinuria reduction with SGLT2 inhibitors in a patient treated with tyrosine kinase inhibitor lenvatinib.

We describe the case of a 66-year-old woman treated with tyrosine kinase inhibitor Lenvatinib for thyroid carcinoma who had persistent proteinuria above 2 g/24 h despite maximal dose of angiotensin-converting enzyme inhibitor. We initiated a treatment with SGLT2 inhibitor Dapagliflozin. Three months after Dapagliflozin initiation, her proteinuria decreased to 1 g/24 h, and after 6 months of follow-up was 0.6 g/24 h. To our knowledge, this is the first case of successful proteinuria reduction with SGLT2i in a patient treated with Lenvatinib. Specific renal effects of SGLT2i seem promising and their effects on tyrosine kinase inhibitor renal adverse effects need to be validated in clinical trials involving cancer patients.

Metabolism of pancreatic neuroendocrine tumors: what can omics tell us?

Introduction: Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature. Methodology: We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs. Results: By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.

Factors Associated with Survival in Anaplastic Thyroid Carcinoma: A Multicenter Study from the ENDOCAN-TUTHYREF Network.

Background: Anaplastic thyroid carcinoma (ATC) is a rare and frequently fatal type of thyroid cancer. The degree of heterogeneity in survival rates for ATC is incompletely studied. This study evaluated the factors associated with overall survival (OS) of patients with ATC using multicenter real-world data from a national tertiary care center network in France. Methods: In this multicenter, retrospective cohort study, all patients with ATC diagnosed between 2010 and 2020 were identified from the national database of the French ENDOCAN-TUTHYREF network. Factors associated with OS were examined in multivariable analyses using Cox proportional hazards models. Results: The study included 360 patients. Of these, 220 (61%) were female and the median age was 72 years (interquartile range: 62-80). The percentages of patients with pure and mixed (synchronously-transformed) ATC (p-ATC and st-ATC) were 62.5% and 26.7%, respectively. The median OS was 6.8 months [confidence interval, CI: 5.5-8.1]: not reached for stage IVa, 11.4 months [8.2-17.8] for IVb, and 4.6 months [3.5-5.7] for IVc. Surgery, radiation therapy to the neck, chemotherapy, and best supportive care were administered to 69 (19.2%), 214 (59.4%), 254 (70.6%), and 66 (18.3%) patients, respectively. In a multivariable analysis, including stage IVb-IVc patients, significantly higher OS was observed in patients with Eastern Cooperative Oncology Group performance-status of 0-1 (hazard ratio [HR], 0.6; [CI, 0.4-0.9], p < 0.02), stage IVb [HR, 0.5; CI, 0.4-0.8, p < 0.001], and multimodal treatment (surgery and chemoradiotherapy) [HR, 0.07; CI, 0.04-0.1, p < 0.001]. Variables associated with significantly worse OS included: p-ATC (vs. st-ATC) [HR, 1.83; CI, 1.33-2.51, p = 0.001] and a neutrophil-to-lymphocyte ratio (NLR) >5.05 [HR, 2.05, CI, 1.39-3.05, p < 0.001]. Conclusions: Factors independently associated with improved OS in ATC included: European Cooperative Oncology Group performance status, disease stage, multimodality treatment, synchronously transformed ATC, and lower NLR. Long-term OS was observed in selected patients with ATC who underwent multimodal treatment.

Prevalence of Endocrine Manifestations and GIST in 108 Systematically Screened Patients With Neurofibromatosis Type 1.

Context: In patients with neurofibromatosis type 1 (NF1), guidelines suggest screening for pheochromocytoma by metanephrine measurement and abdominal imaging, which may lead to the discovery of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and their differential diagnosis, gastrointestinal stromal tumors (GISTs). Other endocrine manifestations such as follicular thyroid carcinoma and primary hyperparathyroidism have also been reported in a few cases. Objective: This study aimed to describe prevalence and clinical presentation of these manifestations through systematic screening in a large cohort of patients. Methods: In this monocentric retrospective study, 108 patients with NF1 were included and screened for endocrine manifestations and GISTs. Clinical, laboratory, molecular profile, pathology, and morphologic (abdominal computed tomography scan and/or magnetic resonance imaging) and functional imaging were collected. Results: Twenty-four patients (22.2% of the cohort, 16 female, mean age 42.6 years) presented with pheochromocytomas that were unilateral in 65.5%, benign in 89.7%, and with a ganglioneural component in 20.7%. Three female patients (2.8% of the cohort, aged 42-63 years) presented with well-differentiated GEP-NETs, and 4 (3.7%) with GISTs. One patient had primary hyperparathyroidism, 1 patient had medullary microcarcinoma, and 16 patients had goiter, multinodular in 10 cases. There was no correlation between pheochromocytoma and other NF1 tumoral manifestations, nor correlations between pheochromocytoma and NF1 genotype, despite a familial clustering in one-third of patients. Conclusion: The pheochromocytoma prevalence in this NF1 cohort was higher (>20%) than previously described, confirming the interest of systematic screening, especially in young women. The prevalence of GEP-NETs and GISTs was about 3%, respectively. No phenotype-genotype correlation was observed.

Cognitive Outcome After Islet Transplantation.

Severe or repeated hypoglycemia events may favor memory complaints in type 1 diabetes (T1D). Pancreatic islet transplantation (IT) is an alternative option to exogenous insulin therapy in case of labile T1D, implying a maintenance immunosuppression regimen based on sirolimus or mycophenolate, associated with tacrolimus, that may also have neurological toxicity. The objective of this study was to compare a cognitive rating scale Mini-Mental State Examination (MMSE) between T1D patients with or without IT and to identify parameters influencing MMSE. Methods: This retrospective cross-sectional study compared MMSE and cognitive function tests between islet-transplanted T1D patients and nontransplanted T1D controls who were transplant candidates. Patients were excluded if they refused. Results: Forty-three T1D patients were included: 9 T1D patients before IT and 34 islet-transplanted patients (14 treated with mycophenolate and 20 treated with sirolimus). Neither MMSE score (P = 0.70) nor higher cognitive function differed between islet versus non-islet-transplanted patients, whatever the type of immunosuppression. In the whole population (N = 43), MMSE score was negatively correlated to glycated hemoglobin (r = -0.30; P = 0.048) and the time spent in hypoglycemia on the continuous glucose monitoring (r = -0.32; P = 0.041). MMSE score was not correlated to fasting C-peptide level, time spent in hyperglycemia, average blood glucose, time under immunosuppression, duration of diabetes, or beta-score (success score of IT). Conclusions: This first study evaluating cognitive disorders in islet-transplanted T1D patients argues for the importance of glucose balance on cognitive function rather than of immunosuppressive treatment, with a favorable effect of glucose balance improvement on MMSE score after IT.

Complete pathological response following chemotherapy and radiotherapy in two cases of advanced anaplastic thyroid carcinoma.

Introduction: Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets. Case presentation: Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair-gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages. Conclusion: We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.

Primary Graft Function and 5 Year Insulin Independence After Pancreas and Islet Transplantation for Type 1 Diabetes: A Retrospective Parallel Cohort Study.

In islet transplantation (ITx), primary graft function (PGF) or beta cell function measured early after last infusion is closely associated with long term clinical outcomes. We investigated the association between PGF and 5 year insulin independence rate in ITx and pancreas transplantation (PTx) recipients. This retrospective multicenter study included type 1 diabetes patients who underwent ITx in Lille and PTx in Nantes from 2000 to 2022. PGF was assessed using the validated Beta2-score and compared to normoglycemic control subjects. Subsequently, the 5 year insulin independence rates, as predicted by a validated PGF-based model, were compared to the actual rates observed in ITx and PTx patients. The study enrolled 39 ITx (23 ITA, 16 IAK), 209 PTx recipients (23 PTA, 14 PAK, 172 SPK), and 56 normoglycemic controls. Mean[SD] PGF was lower after ITx (ITA 22.3[5.2], IAK 24.8[6.4], than after PTx (PTA 38.9[15.3], PAK 36.8[9.0], SPK 38.7[10.5]), and lower than mean beta-cell function measured in normoglycemic control: 36.6[4.3]. The insulin independence rates observed at 5 years after PTA and PAK aligned with PGF predictions, and was higher after SPK. Our results indicate a similar relation between PGF and 5 year insulin independence in ITx and solitary PTx, shedding new light on long-term transplantation outcomes.

Pituitary adenoma & nuclear medicine: Recent outcomes and ongoing developments.

In order to explore pituitary adenoma (PA), magnetic resonance imaging (MRI) remains the cornerstone. However, there are some limitations and MRI can be non-conclusive. The development of additional imaging modalities like nuclear medicine explorations may help to confirm PA diagnosis, guide management and follow up. Nuclear medicine uses radiopharmaceuticals for imaging with single photon emission computed tomography (SPECT), or positron emission tomography (PET), coupled to CT scan. Radiopharmaceuticals products target specific cellular elements which allow to explore several biological pathways. Nuclear medicine may also be used for therapeutic purposes and recent developments of approach based on Peptide Receptor Radionuclide Therapy (PRRT) for treatment of aggressive PA and pituitary carcinoma will be reviewed. Several radiotracers have been studied in the context of PA, and the aim of this paper is to discuss their respective performances and clinical interest.

Impact of Lymph Node Dissection on Postoperative Complications of Total Thyroidectomy in Patients with Thyroid Carcinoma.

Background: Lymph node dissection (LND) in primary treatment of differentiated thyroid carcinoma is controversial. The aim of our retrospective study was to analyse the risk factors of post-thyroidectomy complications and to assess the morbidity of lymph node dissection, especially in the central neck compartment, since prophylactic central lymph node dissection has not been proven to bring an overall survival benefit. Methods: We performed a retrospective analysis of postoperative complications from 1547 consecutive patients with differentiated thyroid carcinoma in an academic department of endocrine surgery over a period of 10 years. Results: A total of 535 patients underwent lymph node dissection, whereas the other 1012 did not. The rate of postoperative hypoparathyroidism was higher in patients with LND (17.6% vs. 11.4%, p = 0.001). No significant difference in the rate of permanent hypoparathyroidism (2.4% vs. 1.3%, p = 0.096) was observed between these two groups. A multivariate analysis was performed. Female gender, ipsilateral and bilateral central LND (CLND), parathyroid autotransplantation, and the presence of the parathyroid gland on the resected thyroid were associated with transient hypoparathyroidism. Bilateral CLND and the presence of the parathyroid gland on specimen were associated with permanent hypoparathyroidism. The rate of transient recurrent laryngeal nerve (RLN) injury (15.3% vs. 5.4%, p < 0.001) and permanent RLN injury (6.5% vs. 0.9%, p < 0.001) were higher in the LND group. In multivariate analysis, ipsilateral and bilateral lateral LND (LLND) were the main predictive factors of transient and permanent RLN injury. Bilateral RLN injury (2.6% vs. 0.4%, p < 0.001), chyle leakage (2.4% vs. 0%, p < 0.001), other nerve injuries (2.2% vs. 0%, p < 0.001), and abscess (2.4% vs. 0.5%, p = 0.001) were higher in the patients with LND. Conclusions: The surgical technique and the extent of lymph node dissection during surgery for thyroid carcinoma increase postoperative morbidity. A wider knowledge of lymph-node-dissection-related complications associated with thyroid surgery could help surgeons to carefully evaluate the surgical and medical therapeutic options.

Serum fatty acid profiling in patients with SDHx mutations: New advances on cellular metabolism in SDH deficiency.

Apart from the oncometabolite succinate, little studies have appeared on extra-mitochondrial pathways in Succinate Dehydrogenase (SDH) genetic deficiency. The role of NADH/NAD+ redox status and dependent pathways was recently emphasized. Therein, fatty acid (FA) metabolism data were collected here in 30 patients with a loss of function (LOF) variant in one SDHx gene (either with a pheochromocytoma/paraganglioma (PPGL) or asymptomatic) and in 22 wild-type SDHx controls (with PPGL or asymptomatic). Blood acylcarnitines in two patients, peroxisomal biomarkers, very long-chain saturated FA (VLCFA), and C20 to C24 n-3 polyunsaturated fatty acids (PUFA), in all patients were measured by mass spectrometry. Preliminary data showed elevated even and odd long- and very long-chain acylcarnitines in two patients with a SDHB variant. In the whole series, no abnormalities were observed in biomarkers of peroxisomal ß-oxidation (C27-bile acids, VLCFAs and phytanic/pristanic acids) in SDHx patients. However, an increased hexaene to pentaene PUFA ratio ([TetraHexaenoic Acid + DocosaHexaenoic Acid]/[n-3 DocosaPentaenoic Acid + EicosaPentaenoic Acid]) was noticed in patients with SDHC/SDHD variants vs patients with SDHA/SDHB variants or controls, suggesting a higher degree of unsaturation of PUFAs. Within the group with a SDHx variant, Eicosapentaenoate/Tetracosahexaenoate ratio, as an empiric index of shortening/elongation balance, discriminated patients with PPGL from asymptomatic ones. Present findings argue for stimulated elongation of saturated FAs, changes in shortening/elongation balance and desaturation rates of C20-C24 PUFAs in SDH-deficient patients with PPGL. Overall, oxidation of NADH sustained by these pathways might reflect or impact glycolytic NAD+ recycling and hence tumor proliferation.

Unexpected cure of a toxic nodule in a multinodular goiter induced by immune checkpoint inhibitors: a case report.

Introduction: Immune checkpoint inhibitors (ICI) are used to treat cancers including metastatic melanomas and can induce endocrine side effects. The thyroid is frequently affected with classically transient thyrotoxicosis followed by hypothyroidism. The evolution of thyroid nodules and goiters under ICI therapy is poorly described. Case presentation: A 72-year-old male presenting with hyperthyroidism due to a toxic nodule in a multinodular goiter (MNG) started ICI therapy combining ipilimumab and nivolumab to treat metastatic melanoma. After an initial worsening of thyrotoxicosis, treated with carbimazole, he developed profound hypothyroidism, persisting after carbimazole discontinuation, needing a long-term levothyroxine supplementation. Ultrasound control performed 6 months after ICIs treatment initiation revealed diffuse thyroid atrophy with involution of all nodules. 123I-scintigraphy confirmed a destructive mechanism. Discussion: The evolution of MNG and toxic nodules is poorly described in patients treated with ICI since systematic US evaluations are lacking. We describe for the first time a toxic nodule cured by ICI therapy inducing destructive thyroiditis. Conclusion: Pre-existing nodules and MNG, even if toxic, are not a contraindication for ICI treatment provided the patients are carefully monitored.

Efficacy of lanreotide 120 mg primary therapy on tumour shrinkage and ophthalmologic symptoms in acromegaly after 1 month.

INTRODUCTION: Few studies have attempted to evaluate the early efficacy of first-generation somatostatin analogues in somatotroph macroadenomas. OBJECTIVE: To investigate the short-term efficacy of primary therapy with lanreotide 120 mg at 1 and 3 months on tumour shrinkage and ophthalmologic symptoms in newly diagnosed patients with acromegaly. DESIGN AND PATIENTS: This single-centre retrospective study included 21 patients with de novo acromegaly resulting from pituitary macroadenoma, with optic chiasm compression (Grade ≤ 2) and/or cavernous sinus invasion, treated with a monthly injection of lanreotide 120 mg. Clinical, hormonal, ophthalmologic and magnetic resonance imaging scan evaluations were conducted after the first and the third months of treatment. RESULTS: Tumour volume reduction was more pronounced at 1 month; mean volume change: -31.4 ± 19.5%, p < .0001 than between the first and third month of treatment; mean volume reduction: -20.6 ± 13.4%, p = .0009. The mean volume change between baseline and the third month was - 46.4 ± 21.6, (p < .0001). A significant volume reduction (≥25%) was observed in 61.9% of individuals (13/21) at the first month. Among 14 individuals with optic chiasm compression and visual field defects, visual field normalization or improvement were observed in seven cases (50%), stabilization in four cases (28.5%), and mild worsening in three cases (21.4%) at 1 month. The decrease in growth hormone and IGF-1 serum values was significant at 1 month. CONCLUSIONS: Primary treatment with lanreotide 120 mg in patients with somatotroph macroadenomas provides early significant tumour shrinkage with rapid improvement of visual symptoms at the end of the first month in 50% of patients.

Anaplastic Thyroid Carcinoma: An Update.

Anaplastic thyroid carcinoma (ATC) is a rare and undifferentiated form of thyroid cancer. Its prognosis is poor: the median overall survival (OS) of patients varies from 4 to 10 months after diagnosis. However, a doubling of the OS time may be possible owing to a more systematic use of molecular tests for targeted therapies and integration of fast-track dedicated care pathways for these patients in tertiary centers. The diagnostic confirmation, if needed, requires an urgent biopsy reread by an expert pathologist with additional immunohistochemical and molecular analyses. Therapeutic management, defined in multidisciplinary meetings, respecting the patient's choice, must start within days following diagnosis. For localized disease diagnosed after primary surgical treatment, adjuvant chemo-radiotherapy is recommended. In the event of locally advanced or metastatic disease, the prognosis is very poor. Treatment should then involve chemotherapy or targeted therapy and decompressive cervical radiotherapy. Here we will review current knowledge on ATC and provide perspectives to improve the management of this deadly disease.

Bone metastases from differentiated thyroid carcinoma: heterogenous tumor response to radioactive Iodine therapy and overall survival.

PURPOSE: Bone metastases (BM) from differentiated thyroid carcinoma (DTC) impact negatively the quality of life and the life expectancy of patients. The aim of the study was (a) to evaluate the overall survival (OS) and prognostic factors of OS and (b) to assess predictive factors of complete BM response (C-BM-R) using radioiodine treatment (RAI) either alone or in association with focal treatment modalities. METHODS: A total of 178 consecutive DTC patients harbouring BM, treated between 1989 and 2015, were enrolled in this retrospective study conducted in two tertiary referral centers. OS analysis was performed for the whole cohort, and only the 145 considered non-RAI refractory patients at BM diagnosis were evaluated for C-BM-R following RAI. RESULTS: The median OS from BM diagnosis was 57 months (IQR: 24-93). In multivariate analysis, OS was significantly reduced in the case of T4 stage, 18FDG uptake by the BM and RAI refractory status. Among the 145 DTC considered non-RAI refractory patients at BM diagnosis, 46 patients (31.7%) achieved a C-BM-R following RAI treatment, either alone in 32 (18%) patients or in association with focal BM treatment modalities in 14. The absence of extra-skeletal distant metastasis and of 18FDG uptake in BM were predictive for C-BM-R. CONCLUSIONS: In nearly one-third of DTC patients with RAI avid BM, RAI alone or in combination with BM focal treatment can induce C-BM-R. The presence of 18FDG uptake in BM is associated with an absence of C-BM-R and with a poor OS. 18FDG PET-CT should be performed when BM is suspected.

The heart, an endocrine gland: Natriuretic peptides.

The natriuretic peptide family consists of three biologically active peptides: atrial natriuretic peptide (ANP), brain (or B-type) natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). ANP and BNP, secreted by the heart, act as cardiac hormones, whereas CNP is an endothelial peptide. The aim of this manuscript is to review the production, action mechanisms, effects and clinical applications of natriuretic peptides.