Genetic testing in prolactinomas: a cohort study.

BACKGROUND: Prolactinomas represent 46%-66% of pituitary adenomas, but the prevalence of germline mutations is largely unknown. We present here the first study focusing on hereditary predisposition to prolactinoma. OBJECTIVE: We studied the prevalence of germline mutations in a large cohort of patients with isolated prolactinomas. MATERIALS AND METHODS: A retrospective study was performed combining genetic and clinical data from patients referred for genetic testing of MEN1, AIP, and CDKN1B between 2003 and 2020. SF3B1 was Sanger sequenced in genetically negative patients. RESULTS: About 506 patients with a prolactinoma were included: 80 with microprolactinoma (15.9%), 378 with macroprolactinoma (74.7%), 48 unknown; 49/506 in a familial context (9.7%). Among these, 14 (2.8%) had a (likely) pathogenic variant (LPV) in MEN1 or AIP, and none in CDKN1B. All positive patients had developed a macroprolactinoma before age 30. The prevalence of germline mutations in patients with isolated macroprolactinoma under 30 was 4% (11/258) in a sporadic context and 15% (3/20) in a familial context. Prevalence in sporadic cases younger than 18 was 15% in men (5/33) and 7% in women (4/57). No R625H SF3B1 germline mutation was identified in 264 patients with macroprolactinomas. CONCLUSIONS: We did not identify any LPVs in patients over 30 years of age, either in a familial or in a sporadic context, and in a sporadic context in our series or the literature. Special attention should be paid to young patients and to familial context.

Polycystic ovary syndrome and adipose tissue.

Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women of reproductive age. Typically, it is associated with ovulatory dysfunction: dysovulation or anovulation, and symptoms of hyperandrogenism. It incurs risk of metabolic disorders such as diabetes, dyslipidemia and fatty liver. As a key endocrine organ in metabolic homeostasis, adipose tissue is often implicated in these complications. Studies of white adipose tissue (WAT) in PCOS have focused on the mechanism of insulin resistance in this tissue. Clinically, abnormalities in WAT distribution are seen, with decreased waist-to-hip ratio and increased ratio of adipose to lean mass. Such abnormalities are greater when total circulating androgens are elevated. At tissue level, white adipocyte hyperplasia occurs, along with infiltration of macrophages. Secretion of adipokines, cytokines and chemo-attractant proteins is increased in a pro-inflammatory manner, leading to reduced insulin sensitivity via alteration of glucose transporters, and hence decreased glucose uptake. The kinetics of non-esterified fatty acids (or free fatty acids) is also altered, leading to lipotoxicity. In recent years, brown adipose tissue (BAT) has been studied in women with PCOS. Although abundance is low in the body, BAT appears to play a significant role in energy expenditure and metabolic parameters. Both supra-clavicular skin temperature, which reflects BAT activity, and BAT mass are reduced in women with PCOS. Moreover, BAT mass and body mass index (BMI) are inversely correlated in patients. In the adipocyte, increased total circulating androgen levels reduce expression of uncoupling protein 1 (UCP1), a key protein in the brown adipocyte, leading to reduced biogenesis and mitochondrial respiration and hence a reduction in post-prandial thermogenesis. BAT is currently being investigated as a possible new therapeutic application.

Pneumocystis pneumonia in patients with Cushing's syndrome: A French multicenter retrospective study.

OBJECTIVE: Pneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not. METHODS: This was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP. RESULTS: Twenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424±1.102nmol/L and urinary free cortisol>10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667±541nmol/L at the onset of PcP (P<0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP. CONCLUSION: High mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.

Prevalence and characteristics of gonadoblastoma in a retrospective multi-center study with follow-up investigations of 70 patients with Turner syndrome and a 45,X/46,XY karyotype.

Introduction: A gonadectomy is currently recommended in patients with Turner syndrome (TS) and a 45,X/46,XY karyotype, due to a potential risk of gonadoblastoma (GB). However, the quality of evidence behind this recommendation is low. Objective: This study aimed to evaluate the prevalence of GB, its characteristics, as well as its risk factors, according to the type of Y chromosomal material in the karyotype. Methods: Our study within French rare disease centers included patients with TS and a 45,X/46,XY karyotype, without ambiguity of external genitalia. Clinical characteristics of the patients, their age at gonadectomy, and gonadal histology were recorded. The regions of the Y chromosome, the presence of TSPY regions, and the percentage of 45,X/46,XY mosaicism were evaluated. Results: A total of 70 patients were recruited, with a median age of 29.5 years (21.0-36.0) at the end of follow-up. Fifty-eight patients had a gonadectomy, at a mean age of 15 ± 8 years. GB was present in nine cases. Two were malignant, which were discovered at the age of 14 and 32 years, without metastases. Neither the percentage of XY cells within the 45,X/46,XY mosaicism nor the number of TSPY copies was statistically different in patients with or without GB (P = 0.37). However, the entire Y chromosome was frequent in patients with GB (6/9). Conclusions: In our study, including a large number of patients with 45,X/46,XY TS, the prevalence of gonadoblastoma is 12.8%. An entire Y chromosome appears as the main risk factor of GB and should favor early gonadectomy. Significant statement: About 10% of patients with TS have a karyotype containing Y chromosomal material: 45,X/46,XY. Its presence is related to the risk of GB. Therefore, a prophylactic gonadectomy is currently recommended in such patients. However, the quality of evidence is low. Our objective was to evaluate the prevalence of GB according to the type of Y-chromosomal material. We found a prevalence of GB of 12.8% in a cohort of 70 TS patients. No sign of hyperandrogenism was observed. The entire Y chromosome was the most frequent type of Y-material in patients with GB. As the prognosis of these tumors was good, a delay of surgery might be discussed.

Position statement on the diagnosis and management of premature/primary ovarian insufficiency (except Turner Syndrome).

Premature ovarian insufficiency (POI) is a rare pathology affecting 1-2% of under-40 year-old women, 1 in 1000 under-30 year-olds and 1 in 10,000 under-20 year-olds. There are multiple etiologies, which can be classified as primary (chromosomal, genetic, auto-immune) and secondary or iatrogenic (surgical, or secondary to chemotherapy and/or radiotherapy). Despite important progress in genetics, more than 60% of cases of primary POI still have no identifiable etiology; these cases are known as idiopathic POI. POI is defined by the association of 1 clinical and 1 biological criterion: primary or secondary amenorrhea or spaniomenorrhea of>4 months with onset before 40 year of age, and elevated follicle-stimulating hormone (FSH)>25IU/L on 2 assays at>4 weeks' interval. Estradiol level is low, and anti-Müllerian hormone (AMH) levels have usually collapsed. Initial etiological work-up comprises auto-immune assessment, karyotype, FMR1 premutation screening and gene-panel study. If all of these are normal, the patient and parents may be offered genome-wide analysis under the "France Génomique" project. The term ovarian insufficiency suggests that the dysfunction is not necessarily definitive. In some cases, ovarian function may fluctuate, and spontaneous pregnancy is possible in around 6% of cases. In confirmed POI, hormone replacement therapy is to be recommended at least up to the physiological menopause age of 51 years. Management in a rare diseases center may be proposed.

Prospective study of dynamic whole-body 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors.

To present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1-5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs.

Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study.

BACKGROUND: The objective of this study was to investigate the association between the onset of TD and treatment efficacy in NSCLC patients who initiated anti-PD-1 blockade (Nivolumab®) and to assess the impact of TD severity and subtype on nivolumab efficacy. MATERIALS AND METHODS: This study was performed at a referral oncology center between July 20, 2015 and June 30, 2018. Patients with histologically confirmed stage IIIB/IV NSCLC in progression after one or two lines of treatment and who initiated Nivolumab were included. Thyroid function (TSH ± fT4, fT3) was monitored and patients were classified according to TD status [TD(+) versus TD(-)], severity [moderate thyroid dysfunction: TSH level between 0.1 and 0.4 or 4.0 and 10 mIU/L and severe thyroid dysfunction: TSH ≤ 0.1 or ≥ 10mUI/L) and subtype (isolated hypothyroidism, isolated hyperthyroidism and hyperthyroidism then hypothyroidism)]. Clinical endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 194 eligible patients, 134 patients (median age, 63 yo; 70.1% male) were included. Forty (29.9%) patients were classified in TD(+) and had a longer OS of 29.8 months (95% CI 18.8-NR) versus 8.1 months (95% CI 5.5-11.5) in TD(-) group (p < 0.001). PFS was also longer (8.7 months (95% CI 5.3-15.1) in TD(+) versus 1.7 months (95% CI 1.6-1.9) in TD(-) group (p < 0.001). In Cox proportional hazards analysis, TD remained an independent predictive factor of OS/PFS. Severity and subtype of TD were not correlated with OS/PFS. CONCLUSIONS: This study suggested that TD induced by Nivolumab appears to be an independent predictive factor of survival, irrespective of TD severity and subtype.

Impact of myo-inositol treatment in women with polycystic ovary syndrome in assisted reproductive technologies.

Polycystic ovary syndrome (PCOS) is marked in 30 to 40% by insulin resistance and hyperandrogenism. Myo-inositol (MI) increases insulin sensitivity, decreases hyperandrogenism and improves the menstrual cycle. Its effect during assisted reproductive technologies (ART) has been studied by many authors. We conducted a review of the literature on the impact of MI administration in PCOS women in assisted reproductive technologies. Myo-inositol is effective in normalizing ovarian function, improving oocyte and embryo quality in PCOS, however further evaluations by large multicentre randomized controlled trials are needed to assess the clinical pregnancy and live birth rates in ART.

Adherence to growth hormone therapy guidelines in a real-world French cohort of adult patients with growth hormone deficiency.

OBJECTIVE: Using real-world data from patients with growth hormone deficiency (GHD), we evaluated whether clinical practice in France adheres to international guidelines regarding somatropin dose adjustment, and assessed the long-term effectiveness and safety of somatropin. METHODS: Data were obtained from a national prospective systematic longitudinal routine follow-up programme of naive/non-naive adults with childhood-onset (CO) or adult-onset (AO) GHD treated with Norditropin® (Novo Nordisk A/S). RESULTS: Between 2003 and 2006, 331 treatment-naive and non-naive adults with severe GHD were enrolled and followed for a median duration of approximately 5 years; 328 patients were available for analysis. At baseline, mean patient age was 39.2 years; median standard deviation score (SDS) for insulin-like growth factor-1 (IGF-1) level was -2.2 in naive patients, subsequently fluctuating between -0.1 and +0.3 SDS during the study period. Mean GH doses ranged between 0.25 and 0.51mg/day (naive patients) and 0.39 and 0.46mg/day (non-naive patients). Despite generally receiving a higher somatropin dose, women (naive/non-naive) tended to have lower IGF-1 levels than men. Median somatropin dose was consistently higher in patients with CO-GHD than patients with AO-GHD. Extreme IGF-1 values (<-2 or >+2 SDS) were not systematically accompanied by somatropin dose adjustments. Waist circumference improved in approximately one third of patients, at a mean 3.5 years. Somatropin was well tolerated; there were no cardiovascular or cerebrovascular events during the 5-year analysis period. CONCLUSION: Current clinical practice of physicians in France follows international guidelines regarding somatropin dose adjustment in adults with GHD. However, dose adjustments are not always sufficient, notably in women, and treatment effects may have been delayed due to low somatropin dose (Clinical trial registration NCT01580605).

Diagnostic value of positron-emission tomography textural indices for malignancy of 18F-fluorodeoxyglucose-avid adrenal lesions.

BACKGROUND: PET Textural indices could have an add-on diagnostic value for diagnosis of malignancy in patients with FDG-avid adrenal lesions. METHODS: Consecutive patients referred for a FDG-PET/CT to our nuclear medicine department from June 2012 to June 2017 were retrospectively screened. Inclusion criteria were: patients with a FDG-avid adrenal lesion (uptake≥liver background); malignant/benign lesion confirmed histologically or with follow-up imaging examination. Pheochromocytomas were not included in the analysis. For each adrenal lesion, 5 quantitative PET parameters (SUVmax, MTV, TLG, TLRmax and TLRmean) were calculated. Thirty-seven textural indices were extracted using LIFEx software®. Diagnostic performance to determine malignancy was assessed with a ROC analysis. Parameters with a significantly AUC>0.5 were selected and groups of highly correlated (r>0.8) parameters were created. A scoring system combining PET and textural indices was examined. RESULTS: PET textural indices were calculated for 53 lesions (37 malignant, 16 benign). Three PET metabolic parameters (SUVmax, TLRmax, TLRmean) and 13 textural indices had an AUC>0.5. Seven groups of highly correlated parameters (r>0.8) were extracted. For PET parameters, SUVmax had the best AUC (0.89 95% CI [0.79-0.98]; cut-off=7.0). For textural indices, ZLNU had the best AUC (0.87 95% CI [0.78-0.96]; cut-off=34.7) and specificity of 100%. Three scores combining the best four textural indices alone (ContrastGLCM, LRHGE, SZE and ZLNU) or with one PET parameters (SUVmax, TLRmax) were developed but did not increase the diagnostic performance (AUC≤0.89). ZLNU was the best parameter to distinguish primary adrenal cancer from adrenal metastases in malignant lesions (P<0.001). CONCLUSIONS: Our study highlighted excellent diagnostic performance of several PET textural indices comparable to that of PET metabolic parameters. However, our results did not find any additional diagnostic value of textural indices when combined with metabolic parameters.

Non-classical effects of vitamin D: Non-bone effects of vitamin D.

Our understanding of vitamin D has improved considerably in recent years. The role of vitamin D in preventing osteoporotic fractures is now well-established. However, an important controversy has emerged in the last decade concerning the effects of the active form of vitamin D (1,25-dihydroxy-vitamin D) on tissues other than bone (non-classical effects). The demonstration that the vitamin D receptor (VDR) is ubiquitously, expressed combined with increasing observational data supporting a relationship between the level of 25-hydroxy-vitamin D in the serum and chronic metabolic disorders, cardiovascular disease and neoplasms, have led to its redefinition as a steroid hormone and the proposal of its use in preventing and/or treating those diseases. This article is an update on the different non-bone or non-classical effects of "vitamin-hormone D", and its potential preventive or therapeutic role in certain diseases, however, this review is not exhaustive. The different modalities of substitution or supplementation proposed in France by the Groupe de Recherche et d'Information sur les Ostéoporoses (GRIO) are also summarised.

Clinical Assessment of 177Lu-DOTATATE Quantification by Comparison of SUV-Based Parameters Measured on Both Post-PRRT SPECT/CT and 68Ga-DOTATOC PET/CT in Patients With Neuroendocrine Tumors: A Feasibility Study.

PATIENTS AND METHODS: Patients with WD-GEP-NET who benefited from a pretherapeutic 68Ga-DOTATOC PET/CT and a 177Lu-DOTATATE SPECT/CT after the cycle 1 of peptide receptor radionuclide therapy were prospectively included. SPECT/CT acquisitions were performed on a system calibrated with a conversion factor of 9.48 counts/MBq per second and were reconstructed with an iterative algorithm allowing quantification using the SPECTRA Quant software (MIM Software, Cleveland, OH). For each patient, different SUV parameters were recorded on both PET/CT (Ga parameters) and SPECT/CT (Lu parameters) for comparison: physiological uptakes (liver/spleen), tumor uptake (1-10/patient; SUVmax, SUVmean, SUVpeak, MTV), tumor-to-liver and tumor-to-spleen ratios according to liver/spleen SUVmax and SUVmean (TLRmax, TLRmean, TSRmax, and TSRmean, respectively). RESULTS: Ten patients (8 female; 2 male) aged from 50 to 83 years presenting with a metastatic progressive WD-GEP-NET (7 small intestine, 2 pancreas, 1 rectum) were included. Median values of lesional Lu-SUV were significantly lower than the corresponding Ga-SUV (P < 0.001), whereas median values of lesional Lu-MTV, Lu-TLR, and Lu-TSR were significantly higher than the corresponding Ga-MTV, Ga-TLR, and Ga-TSR (P < 0.02). Pearson correlation coefficients were strong for both SUV and MTV parameters (0.779-0.845), weak for TLR parameters (0.365-0.394), and moderate-to-strong for TSR parameters (0.676-0.750). CONCLUSIONS: Our results suggest the feasibility of 177Lu-DOTATATE SPECT/CT quantification in clinical practice and show a strong correlation of several SUV-based parameters with the corresponding in 68Ga-DOTATOC PET/CT.

Diagnostic performance of a whole-body dynamic 68GA-DOTATOC PET/CT acquisition to differentiate physiological uptake of pancreatic uncinate process from pancreatic neuroendocrine tumor.

To evaluate the diagnostic performance of net influx rate (Ki) values from a whole-body dynamic (WBD) Ga-DOTATOC-PET/CT acquisition to differentiate pancreatic neuroendocrine tumors (pNETs) from physiological uptake of pancreatic uncinate process (UP).Patients who were benefited from a WBD acquisition for the assessment of a known well-differentiated neuroendocrine tumor (NET)/suspicion of disease in the prospective GAPET-NET cohort were screened. Only patients with a confirmed pNET/UP as our gold standard were included. The positron emission tomography (PET) procedure consisted in a single-bed dynamic acquisition centered on the heart, followed by a whole-body dynamic acquisition and then a static acquisition. Dynamic (Ki calculated according to Patlak method), static (SUVmax, SUVmean, SUVpeak) parameters, and tumor-to-liver and tumor-to-spleen ratio (TLRKi and TSRKi (according to hepatic/splenic Ki)), tumor SUVmax to liver SUVmax (TM/LM), tumor SUVmax to liver SUVmean (TM/Lm), tumor SUVmax to spleen SUVmax (TM/SM), and tumor SUVmax to spleen SUVmean (TM/Sm) (according to hepatic/splenic SUVmax and SUVmean respectively) were calculated. A Receiver Operating Characteristic (ROC) analysis was performed to evaluate their diagnostic performance to distinguish UP from pNET.One hundred five patients benefited from a WBD between July 2018 and July 2019. Eighteen (17.1%) had an UP and 26 (24.8%) a pNET. For parameters alone, the Ki and SUVpeak had the best sensitivity (88.5%) while the Ki, SUVmax, and SUVmean had the best specificity (94.4%). The best diagnostic accuracy was obtained with Ki (90.9%). For ratios, the TLRKi and the TSRKi had the best sensitivity (95.7%) while the TM/SM and TM/Sm the best specificity (100%). TLRKi had the best diagnostic accuracy (95.1%) and the best area under the curve (AUC) (0.990).Our study is the first one to evaluate the interest of a WBD acquisition to differentiate UP from pNETs and shows excellent diagnostic performances of the Ki approach.

Le syndrome des ovaires polykystiques : quelles nouveautés en 2019 ?: Keeping up with PCOS in 2019.

PolyCystic Ovary Syndrome (PCOS) is the first endocrinopathy of women of child-bearing age and the leading cause of anovulatory infertility. The pathophysiology of this syndrome is complex and involves genetic traits highlighted by GWAS and epigenetic traits with DNA methylation modifications. Initially described as an ovarian disease, works carried out over recent years were turned towards neuroendocrine disorder involving GABAergic pathways, KNDy neurons and a possible role of prenatal androgen exposure determined by animal models. Clinically, PCOS leads to many complications including psychological and emotional disorders demonstrated in large populations of PCOS women. © 2019 Published by Elsevier Masson SAS. All rights reserved. Cet article fait partie du numéro supplément Les Must de l'Endocrinologie 2019 réalisé avec le soutien institutionnel de Ipsen-Pharma.

Efficacy and safety of high-dose long-acting repeatable octreotide as monotherapy or in combination with pegvisomant or cabergoline in patients with acromegaly not adequately controlled by conventional regimens: results of an open-label, multicentre study.

INTRODUCTION: Long-acting repeatable (LAR) octreotide i.m. is a potent, synthetic somatostatin analogue (SSA) that requires less frequent dosing and offers quality of life (QoL) benefits in acromegaly patients compared to its shorter-acting predecessor. This study investigated the efficacy and safety of high-dose Sandostatin® LAR® as monotherapy or in combination with pegvisomant or cabergoline in acromegalic patients with pituitary adenomas following previous failure of conventional SSA treatment. MATERIAL AND METHODS: After three months of high-dose Sandostatin® LAR® monotherapy (40 mg), patients who achieved biochemical control (n = 7) continued to receive the same treatment for an additional four months, whereas uncontrolled patients were randomised to receive high-dose Sandostatin® LAR® in combination with pegvisomant (n = 31) or cabergoline (n = 32). Outcomes included biochemical response at eight months, QoL, and safety. RESULTS: After three months, 3 of 68 (4.4%) evaluable patients achieved a biochemical control (BC) as assessed by levels of growth hormone and insulin-like growth factor-1. At eight months, 4 of 67 (6.0%) patients achieved BC, including one receiving monotherapy and three receiving Sandostatin® LAR® plus cabergoline. Partial response rate, improvements in acromegaly signs and symptoms, and changes in QoL were similar for all three groups. All treatments were well tolerated with a slight excess of adverse events in the combination arms. There were no deaths or serious adverse events leading to treatment discontinuation. CONCLUSION: These data demonstrate that high-dose Sandostatin® LAR® as monotherapy or in combination with pegvisomant or cabergoline is a feasible salvage option in patients with pituitary adenomas not adequately controlled on conventional SSA regimens.

Diagnostic Value of FDG PET-CT Quantitative Parameters and Deauville-Like 5 Point-Scale in Predicting Malignancy of Focal Thyroid Incidentaloma.

Objective: To evaluate the diagnostic value of FDG PET-CT metabolic parameters and Deauville-like 5 point-scale to predict malignancy in a population of patients presenting focal thyroid incidentaloma (fTI). Design: This retrospective study included 41 fTI, classified according to cytological and histological data as benign (BL) or malignant lesion (ML). FDG PET-CT semi-quantitative parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG), tumor to liver SUVmean ratio (TLRmax and TLRmean), tumor to blood-pool SUVmean ratio (TBRmax and TBRmean) were calculated. Each fTI was also classified on a Deauville-like 5-point scale (DS) currently used in lymphoma. Comparison between BL and ML was performed for each parameter and a ROC analysis was conducted. Results: All quantitative PET metabolic parameters (SUV parameters, volume based parameters and SUV ratio) were higher in ML compared with BL, yet no significant difference was reported. fTI (uptake) malignancy rate according to DS grades 2, 3, 4, and 5 was, respectively, 25% (1 of 4), 28.6% (2 of 7), 8.3% (1 of 12), and 33.3% (6 of 18) with no significant difference between ML and BL groups. Results of ROC analysis showed that mean TBR had the highest AUC in our cohort (0.66 95%CI [0.41; 0.91]) with a cut-off value of 2.2. Specificity of MTV and TLG was 100% (cut-off values: MTV 9.6 ml, TLG 22.9 g) and their sensitivity was 30 and 40%, respectively. Conclusion: Our study did not highlight any FDG PET/CT parameter predictor of fTI malignancy.

Clinical Validation of a Pixon-Based Reconstruction Method Allowing a Twofold Reduction in Planar Images Time of 111In-Pentetreotide Somatostatin Receptor Scintigraphy.

OBJECTIVE: The objective of this study was to evaluate the diagnostic efficacy of Pixon-based reconstruction method on planar somatostatin receptor scintigraphy (SRS). METHODS: All patients with neuroendocrine tumors (NETs) disease who were referred for SRS to our department during 1-year period from January to December 2015 were consecutively included. Three nuclear physicians independently reviewed all the data sets of images which included conventional images (CI; 15 min/view) and processed images (PI) obtained by reconstructing the first 450 s extracted data using Oncoflash® software package. Image analysis using a 3-point rating scale for abnormal uptake of 111 Indium-DTPA-Phe-octreotide in any lesion or organ was interpreted as positive, uncertain, or negative for the evidence of NET disease. A maximum grade uptake of the radiotracer in the lesion was assessed by the Krenning scale method. The results of image interpretation by the two methods were considered significantly discordant when the difference in organ involvement assessment was negative vs. positive or in lesion uptake was ≥2 grades. Agreement between the results of two methods and by different scan observers was evaluated using Cohen κ coefficients. RESULTS: There was no significant (p = 0.403) correlation between data acquisition protocol and quality image. The rates of significant discrepancies for exam interpretation and organs involvement assessment were 2.8 and 2.6%, respectively. Mean κ values revealed a good agreement for concordance between CI and PI interpretation without difference of agreement for inter/intra-observer analysis. CONCLUSION: Our results suggest the feasibility to use a Pixon-based reconstruction method for SRS planar images allowing a twofold reduction of acquisition time and without significant alteration of image quality or on image interpretation.

Malignancy rate of focal thyroid incidentaloma detected by FDG PET-CT: results of a prospective cohort study.

OBJECTIVE: To evaluate the malignancy rate of focal thyroid incidentaloma (fTI) in a population of patients undergoing a 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) for a non-thyroid purpose. DESIGN: We conducted a prospective cohort study from January 2013 to November 2014. All consecutive patients referred for a FDG PET-CT were prospectively screened. Patients with known neoplastic thyroid disease were excluded from the analysis. All patients presenting one or more fTI and who accepted to benefit from a complementary thyroid ultrasonography (US) were included and managed according to the French endocrine society consensus. Prevalence of fTI in our population and malignancy rate was assessed. RESULTS: During the inclusion period, 10,171 patients were referred for a FDG PET-CT in our center. Fifty-three patients presenting a known thyroid disease were excluded. Among the remaining 10,118 patients, 127 (1.3%) with 131 fTI were individualized. US could not be performed in 37 patients. The remaining 90 patients (92 fTI) were explored by US ± fine-needle aspiration biopsy (FNAB). US results demonstrated a nodule aspect in 80 cases of which 60 benefited from FNAB. Nineteen of 92 fTI underwent surgery with 10 malignant lesions among the 60 patients performing both US and FNAB. CONCLUSION: The prevalence of fTI discovered on FDG PET-CT in our population was 1.3% with 10 malignant lesions among the 60 patients performing both US and FNAB.

Oral and vulvo-vaginal lichenoid reactions due to mitotane (Lysodren): A case report.

BACKGROUND: The purpose of pharmacovigilance (drug safety) is collection, detection, assessment, monitoring, and prevention of adverse effects with pharmaceutical products. It is meant to identify, characterize, prevent, or minimize actual or potential risks relating to medicinal products. To prevent these adverse effects and improve our practice, health professionals have a duty to report side effects to assess this risk and evaluate the benefit/risk requirements. Mitotane (Lysodren) is used for treating adrenocortical carcinoma. Currently, no side effects concerning oral and genital mucosa have been reported. CASE SUMMARY: This case report is about a 50 years old woman. Six months after the initiation on mitotane treatment, she developed erosive lesions located on the oral and vaginal mucosa. These drug reactions were diagnosed as erosive lichen planus by the biopsy. This lichenoid lesions were resistant to the usual treatments, mitotane being at the time not replaceable. CONCLUSION: This case describes an unreported adverse effect of mitotane, it is - to our knowledge - the 1st description of erosive lichenoid drug reaction due to Mitotane.

DNA Methylation Is an Independent Prognostic Marker of Survival in Adrenocortical Cancer.

CONTEXT: Adrenocortical cancer (ACC) is an aggressive tumor with a heterogeneous outcome. Prognostic stratification is difficult even based on tumor stage and Ki67. Recently integrated genomics studies have demonstrated that CpG islands hypermethylation is correlated with poor survival. OBJECTIVE: The goal of this study was to confirm the prognostic value of CpG islands methylation on an independent cohort. DESIGN: Methylation was measured by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). SETTING: MS-MLPA was performed in a training cohort of 50 patients with ACC to identify the best set of probes correlating with disease-free survival (DFS) and overall survival (OS). These outcomes were validated in an independent cohort from 21 ENSAT centers. PATIENTS: The validation cohort included 203 patients (64% women, median age 50 years, 80% localized tumors). MAIN OUTCOME MEASURES: DFS and OS. RESULTS: In the training cohort, mean methylation of 4 genes (PAX5, GSTP1, PYCARD, PAX6) was the strongest methylation marker. In the validation cohort, methylation was a significant prognostic factor of DFS (P < 0.0001) and OS (P < 0.0001). Methylation, Ki67, and ENSAT stage were combined in multivariate models. For DFS, methylation (P = 0.0005) and stage (P < 0.0001) but not Ki67 (P = 0.19) remained highly significant. For OS, methylation (P = 0.0006), stage (P < 0.0001), and Ki67 (P = 0.024) were independent prognostic factors. CONCLUSIONS: Tumor DNA methylation emerges as an independent prognostic factor in ACC. MS-MLPA is readily compatible with clinical routine and should enhance our ability for prognostication and precision medicine.