Publications by authors named "Helene Lasolle"

17 Publications

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Letter to the editor from Helene Lasolle: "USP8 and TP53 drivers are associated with CNV in a corticotroph adenoma cohort enriched for aggressive tumors".

J Clin Endocrinol Metab 2021 Apr 5. Epub 2021 Apr 5.

Fédération d'Endocrinologie, Hospices Civils de Lyon, Groupement Hospitalier Est, Bron, France.

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http://dx.doi.org/10.1210/clinem/dgab217DOI Listing
April 2021

Chromosomal instability in the prediction of pituitary neuroendocrine tumors prognosis.

Acta Neuropathol Commun 2020 11 10;8(1):190. Epub 2020 Nov 10.

Fédération d'endocrinologie, Centre de Référence des Maladies Rares Hypophysaires, Groupement Hospitalier Est, Hospices Civils de Lyon, 8 av Doyen Lepine, 69677, Bron Cedex, France.

The purpose of this study was to analyze the impact of copy number variations (CNV) on sporadic pituitary neuroendocrine tumors (PitNETs) prognosis, to identify specific prognosis markers according to the known clinico-pathological classification. CGH array analysis was performed on 195 fresh-frozen PitNETs (56 gonadotroph, 11 immunonegative, 56 somatotroph, 39 lactotroph and 33 corticotroph), with 5 years post-surgery follow-up (124 recurrences), classified according to the five-tiered grading classification (invasion, Ki-67, mitotic index and p53 positivity). Effect of alterations on recurrence was studied using logistic regression models. Transcriptomic analysis of 32 lactotroph tumors was performed. The quantity of CNV was dependent on tumor type: higher in lactotroph (median(min-max) = 38% (0-97) of probes) compared to corticotroph (11% (0-77)), somatotroph (5% (0-99)), gonadotroph (0% (0-10)) and immunonegative tumors (0% (0-17). It was not predictive of recurrence in the whole cohort. In lactotroph tumors, genome instability, especially quantity of gains, significantly predicted recurrence independently of invasion and proliferation (p-value = 0.02, OR = 1.2). However, no specific CNV was found as a prognostic marker. Transcriptomic analysis of the genes included in the CNV and associated with prognosis didn't show significantly overrepresented pathway. In somatotroph and corticotroph tumors, USP8 and GNAS mutations were not associated with genome disruption or recurrence respectively. To conclude, CGH array analysis showed genome instability was dependent on PitNET type. Lactotroph tumors were highly altered and the quantity of altered genome was associated with poorer prognosis though the mechanism is unclear, whereas gonadotroph and immunonegative tumors showed the same 'quiet' profile, leaving the mechanism underlying tumorigenesis open to question.
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http://dx.doi.org/10.1186/s40478-020-01067-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653703PMC
November 2020

Age- and Sex-Specific TSH Upper-Limit Reference Intervals in the General French Population: There Is a Need to Adjust Our Actual Practices.

J Clin Med 2020 Mar 14;9(3). Epub 2020 Mar 14.

Hospices Civils de Lyon, Fédération d'Endocrinologie, Groupement Hospitalier Est, F-69677 Bron cedex, France.

It is well known that thyroid dysfunction increases with age. This study is aimed to determine reference intervals, in males and females, suitable for thyroid disease exploration during adult life using routinely collected serum thyrotropin (TSH) data in a tertiary center from 2007 to 2018. Over 11 years, 295,775 TSH levels were measured in a single lab. Among the 156,025 TSH results available for analysis, 90,538 values were from female subjects, 82,019 were from patients aged >60 years and 26,825 were from patients aged >80 years. By using an indirect approach, we determined reference values of TSH adapted to age and sex, and we then evaluated the proportion of patients who would have been reclassified with these reference values. The median TSH ranged from 1.2-1.4 mUI/L during the study period. The upper limit of reference range of TSH increased with age; in females the median to 97.5th percentile values increased continuously from the age of 30 years to the oldest age group. Using new calculated reference values in patients with TSH above the conventional upper-limit reference value (4 mUI/L), the proportion of results reclassified as within the reference interval among patients aged >60 years ranged, according to age group, from 50.5% to 65.1% of females and from 33.0% to 37.7% of males. The use of TSH age-specific and sex-specific upper-limit reference values led to the reclassification of a great number of samples, notably among women. This suggests that age-specific TSH upper-limit reference intervals in daily practice should be used in order to avoid misclassification.
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http://dx.doi.org/10.3390/jcm9030792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141356PMC
March 2020

SST5 expression and USP8 mutation in functioning and silent corticotroph pituitary tumors.

Endocr Connect 2020 Feb 1. Epub 2020 Feb 1.

H Lasolle, Service d'Endocrinologie, Centre de Référence des Maladies Rares de l'Hypophyse HYPO, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.

Objective: Somatostatin receptor type 5 (SST5) is inconsistently expressed by corticotroph tumors, with higher expression found in corticotropinomas having ubiquitin-specific protease 8 (USP8) mutations. Aims were to study the correlation between characteristics of corticotropinomas and SST5 expression/USP8 mutation status and to describe the response to pasireotide in 5 patients.

Design: Retrospective cohort study.

Methods: Clinico-biochemical, radiological and pathological data of 62 patients, operated for a functioning or silent corticotropinoma between 2013 and 2017, were collected. SST5 expression was measured by immunohistochemistry (clone UMB-4, Abcam, IRS>1 being considered positive) and Sanger sequencing was performed on 50 tumors to screen for USP8 mutations.

Results: SST5 expression was positive in 26/62 pituitary tumors. A moderate or strong IRS was found in 15/58 corticotropinomas and in 13/35 functioning corticotropinomas. Among functioning tumors, those expressing SST5 were more frequent in women (22/24 vs 9/15, P=0.04) and had a lower grade (P=0.04) compared to others. USP8 mutations were identified in 13/50 pituitary tumors and were more frequent in functioning compared to silent tumors (11/30 vs 2/20, P=0.05). SST5 expression was more frequent in USP8mut vs USP8wt tumors (10/11 vs 7/19, P=0.007). Among treated patients, normal urinary free cortisol levels were obtained in 3 patients (IRS 0, 2, 6) while a 4-fold decrease was observed in one patient (IRS 4).

Conclusion: SST5 expression appears to be associated with functioning, USP8mut and lower grade corticotropinomas. A correlation between SST5 expression or USP8mut and response to pasireotide remains to be confirmed.
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http://dx.doi.org/10.1530/EC-20-0035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077525PMC
February 2020

Aggressive prolactinomas: how to manage?

Pituitary 2020 Feb;23(1):70-77

INSERM U1052, CNRS UMR5286, Cancer Research Center of Lyon, 69008, Lyon, Auvergne-Rhône-Alpes, France.

Purpose: Aggressive prolactinomas are defined as radiologically invasive tumors which cannot be cured by surgery, and that have an unusually rapid rate of tumor growth despite dopamine agonist treatment and surgery. In some cases, metastasis occurs, defining prolactin carcinoma which is the second most frequent pituitary carcinoma.

Methods: A literature search was performed to review the available data on the treatment of aggressive pituitary prolactinomas or carcinomas.

Results: When optimal standard therapies (high dose cabergoline, surgery and radiotherapy) failed, temozolomide, an alkylating drug, is currently the best option, allowing to control tumor growth in about 50% of treated prolactinomas and improving overall survival of these patients. However, long-term complete response occurs in a limited subgroup of tumors. Alternative drugs could be discussed in a subset of aggressive prolactinomas either before temozolomide (pasireotide, peptide receptor radionuclide therapy…) or after temozolomide failure.

Conclusion: Despite the significant improvement obtained with the use of temozolomide, a need for alternative drugs persists since a majority of these tumors are resistant or will recur during the follow-up. Patients suffering from such a rare condition should have access to clinical trials available for other types of rare cancers, such as tyrosine kinase inhibitors or immunotherapy.
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http://dx.doi.org/10.1007/s11102-019-01000-7DOI Listing
February 2020

Pasireotide-LAR in acromegaly patients treated with a combination therapy: a real-life study.

Endocr Connect 2019 Oct;8(10):1383-1394

Service d'endocrinologie, diabète et nutrition, Hôpital Haut Lévêque, CHU de Bordeaux, Bordeaux, France.

Purpose: Little data are available regarding the safety and efficacy of switching to Pasireotide-LAR monotherapy in acromegaly patients with partial resistance to first-generation somatostatin agonists (1gSRL) who require combination treatment with cabergoline or pegvisomant.

Method: In this monocentric prospective study within a tertiary university hospital, 15 consecutive acromegalic adults partially resistant to 1gSRL treated with octreotide LAR or lanreotide SR, and cabergoline (n = 4, 3.5 mg/week) or pegvisomant (n = 11, median dose 100 mg/week), were switched to Pasireotide-LAR (8 with 40 mg/month; 7 with 60 mg/month). Immunohistochemical expression level of SSTR5 and the granulation pattern of nine somatotroph adenomas were retrospectively determined to test for a correlation with the therapeutic efficacy of Pasireotide-LAR.

Results: Median IGF-1 concentration at the first evaluation (median 3 months) was similar to baseline (1.0 vs 1.1 ULN). 11/15 patients had IGF-1 levels ≤1.3 ULN before and after the switch but individual changes were variable. Hyperglycemia was frequent and greater in diabetic patients. 7/15 patients stopped Pasireotide-LAR due to lack of control of IGF-1 or intolerance. 8/15 patients received Pasireotide-LAR for a median of 29 months with IGF-1 levels ≤1.3 ULN and acceptable glucose tolerance (median HbA1c 6.1%). Two patients required initiation of oral antidiabetic treatment. The intensity of SSTR5 expression and the granulation pattern of adenomas were of limited value for the prediction of Pasireotide-LAR effectiveness.

Conclusion: Pasireotide-LAR may represent a suitable therapeutic alternative in a subset of acromegalic patients requiring combination therapy involving a 1gSRL.
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http://dx.doi.org/10.1530/EC-19-0332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790898PMC
October 2019

Diagnosis, pathology, and management of TSH-secreting pituitary tumors. A single-center retrospective study of 20 patients from 1981 to 2014.

Ann Endocrinol (Paris) 2019 Sep 26;80(4):216-224. Epub 2019 Jul 26.

Université de Lyon, Lyon1, 69372 Lyon, France; Inserm U1052, CNRS UMR5286, Cancer Research Center of Lyon, Lyon, France; Fédération d'endocrinologie, centre de référence maladies rares hypophysaire HYPO, groupement hospitalier Est, hospices Civils de Lyon, 59, boulevard Pinel, 69677 Bron cedex, France. Electronic address:

TSH (thyroid-stimulating hormone)-secreting tumors are the rarest type of pituitary tumor. The objective of this study was to describe initial presentation and follow-up in patients presenting TSH-secreting tumors and to characterize the pathological features, based on a cohort of 20 patients treated in our referral center, between 1981 and 2014. Most of the patients (75%) were female, aged around 50 years (mean: 50±13 years). Initial symptoms were hyperthyroidism (8/20) and/or tumor mass-related symptoms. Median time to diagnosis was 18 months. Biochemical hyperthyroidism was found in 15 patients. Most of the tumors were macroadenomas (75%) and 30% were invasive. Seventeen patients underwent transsphenoidal surgery. All tumors expressed TSH, with>50% positive cells. Eleven were monohormonal and 6 plurihormonal, expressing βTSH plus growth hormone (GH) and/or prolactin (PRL). Both subtypes showed high expression of Pit-1 and SSTR somatostatin receptors. SSTR was slightly expressed in the plurihormonal subtype. Ki-67 index was elevated (≥3%) in only one tumor. Signs of hyperthyroidism were more frequent in the plurihormonal than in the monohormonal subtype. At final follow-up (median: 34.79±66.7 months), 75% of the patients were in complete remission after surgery; persistent hyperthyroidism was controlled by somatostatin analogs, alone (n=3) or associated to radiotherapy (n=1). The multidisciplinary approach promoted early diagnosis and control of hyperthyroidism by neurosurgical treatment, associated to somatostatin analogs or not. Clinical/pathological correlations highlighted the variations in immune profiles and in clinical and biological symptoms.
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http://dx.doi.org/10.1016/j.ando.2019.06.006DOI Listing
September 2019

Emerging and Novel Treatments for Pituitary Tumors.

J Clin Med 2019 Jul 25;8(8). Epub 2019 Jul 25.

INSERM U1052, CNRS UMR5286, Cancer Research Center of Lyon, 28 Laennec Street, 69008 Lyon, France.

A subset of pituitary neuroendocrine tumors (PitNETs) have an aggressive behavior, showing resistance to treatment and/or multiple recurrences in spite of the optimal use of standard therapies (surgery, conventional medical treatments, and radiotherapy). To date, for aggressive PitNETs, temozolomide (TMZ) has been the most used therapeutic option, and has resulted in an improvement in the five-year survival rate in responders. However, given the fact that roughly only one third of patients showed a partial or complete radiological response on the first course of TMZ, and even fewer patients responded to a second course of TMZ, other treatment options are urgently needed. Emerging therapies consist predominantly of peptide receptor radionuclide therapy (20 cases), vascular endothelial growth factor receptor-targeted therapy (12 cases), tyrosine kinase inhibitors (10 cases), mammalian target of rapamycin (mTOR) inhibitors (six cases), and more recently, immune checkpoint inhibitors (one case). Here, we present the available clinical cases published in the literature for each of these treatments. The therapies that currently show the most promise (based on the achievement of partial radiological response in a certain number of cases) are immune checkpoint inhibitors, peptide receptor radionuclide therapy, and vascular endothelial growth factor receptor-targeted therapy. In the future, further improvement of these therapies and the development of other novel therapies, their use in personalized medicine, and a better understanding of combination therapies, will hopefully result in better outcomes for patients bearing aggressive PitNETs.
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http://dx.doi.org/10.3390/jcm8081107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723109PMC
July 2019

Pheochromocytoma, paragangliomas, and pituitary adenoma: An unusual association in a patient with an SDHD mutation. Case report.

Medicine (Baltimore) 2019 Jul;98(30):e16594

Department of Endocrinology, Hospices Civils de Lyon, Fédération d'Endocrinologie.

Rationale: Pituitary adenomas and paragangliomas are both rare endocrine diseases. Paragangliomas (PGL)/pheochromocytomas (PHEO) are part of an inherited syndrome in about 30% to 40% of cases. Among familial cases, mutations of the succinate dehydrogenase (SDH) subunit genes (succinate dehydrogenase subunit [SDH]B, SDHC, SDHD, succinate dehydrogenase subunit AF2 [SDHAF2] , and SDHA) are the most common cause.

Patient Concerns: We here report a 31-year-old patient with a known SDHD mutation whose disease has been revealed by a left PHEO during childhood and who presented at age 29 years a large paraganglioma of the right jugular foramen, a concomitant PHEO of the left adrenal and 2 retroperitoneal paragangliomas. A pituitary incidentaloma was found during investigations on a fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET).

Diagnosis: A pituitary magnetic resonance imaging (MRI) confirmed the presence of a 14 mm pituitary macroadenoma. The pituitary function was normal except for hypogonadotropic hypogonadism. On examination of the fundus, a diagnosis of Pseudo Foster-Kennedy syndrome was made due to a venous compression of the right jugular vein caused by the paraganglioma (PGL). The pituitary adenoma was not compressive to the optic chiasm.

Interventions: A treatment with acetazolamide was started in order to improve intracranial hypertension. The patient couldn't benefit of a surgical approach for the paraganglioma of the right jugular foramen; the patient has been treated with stereotactic radiosurgery (Gamma Knife).

Outcomes: The most recent MRI revealed that the right jugular foramen PGL is stable and the latest visual assessment demonstrated stability despite a recent reduction in acetazolamide dosage. A surveillance by MRI of the pituitary adenoma has been planned.

Lessons: The association of a pituitary adenoma to paragangliomas within a same patient is very uncommon and raises the question of related physiopathological mechanisms.
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http://dx.doi.org/10.1097/MD.0000000000016594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6708967PMC
July 2019

Confirmation of a new therapeutic option for aggressive or dopamine agonist-resistant prolactin pituitary neuroendocrine tumors.

Eur J Endocrinol 2019 Aug;181(2):C1-C3

Fédération d'Endocrinologie, Centre de Référence Maladies Rares Hypophysaires (HYPO), Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.

Recent publications suggested that pasireotide could be a good therapeutic option in some dopamine-resistant or aggressive prolactinomas. We discussed the two published cases and describe another case of poorly differentiated plurihormonal PIT-1-positive adenoma with moderate SSTR2 expression and intense STTR5 expression successfully treated with PAS-LAR 40 mg/month.
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http://dx.doi.org/10.1530/EJE-19-0359DOI Listing
August 2019

Pasireotide: A potential therapeutic alternative for resistant prolactinoma.

Ann Endocrinol (Paris) 2019 Apr 25;80(2):84-88. Epub 2018 Sep 25.

Centre de référence maladies rares hypophysaires (HYPO), fédération d'endocrinologie, groupement hospitalier Est, hospices civils de Lyon, 69677 Bron, France; Faculté de médecine Lyon Est, université Lyon 1, 69372 Lyon, France; Inserm U1052, CNRS UMR5286, Cancer Research Centre of Lyon, 69372 Lyon, France. Electronic address:

Context: About 10% of prolactinomas are resistant to dopamine-agonists (DAs). The only alternatives for tumor and prolactin control are surgery or radiotherapy. While studies on first generation somatostatin analogs have shown no efficacy against prolactinomas, no study has been conducted on the new multireceptor-targeted somatostatin receptor ligand pasireotide, which presents high affinity for 5, 3, 2 and 1 receptor subtypes.

Case Description: A 41 year-old woman presented with a macroprolactinoma showing resistance to all available DAs. She was first diagnosed at 17 years old after which she had undergone two incomplete debulking surgeries. Under pasireotide long-acting release (LAR) treatment, plasma prolactin levels normalized and symptoms disappeared within one month after initiation. The clinical benefits of the monotherapy (specifically, prolactin levels within normal range and stable tumor volume) were maintained for seven years. Glucose tolerance was satisfactory. Pathological analysis of the tumor revealed high SSTR5 and low SSTR2 expression (25 and 5% of cells respectively).

Conclusion: This is a promising first report of a patient with a DA-resistant macroprolactinoma who achieved long-term control, in terms of prolactin normalization and tumor volume, under pasireotide treatment alone. Pasireotide could thus be an alternative in prolactinomas resistant to DA. SSTR expression analysis on pathology could guide patient selection.
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http://dx.doi.org/10.1016/j.ando.2018.07.013DOI Listing
April 2019

Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer.

Thyroid 2018 09;28(9):1174-1179

8 Service de Médecine Nucléaire et de Cancérologie Endocrinienne, Institut Gustave Roussy , Villejuif et Université Paris Saclay, France .

Background: Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is frequent in advanced follicular (FTC) and poorly differentiated thyroid (PDTC) carcinomas and has been implicated in oncogenesis and tumor progression. This study investigated the efficacy and safety of buparlisib, a pan-PI3K inhibitor in radioiodine refractory FTC and PDTC.

Methods: The primary endpoint of this open-label, multicenter, phase 2 pilot study was progression-free survival (PFS) at 6 months. The sample size was determined considering that a PFS ≤50% at 6 months would denote an absence of benefits (null hypothesis). Secondary endpoints were objective response rate, PFS at 12 months, overall survival at 6 and 12 months, and safety based on the frequency and severity of adverse events (AEs).

Results: Forty-three patients (19M/24 F; median age: 67 years) with metastatic, radioiodine refractory, progressive disease received buparlisib, 100 mg, daily. Histology was PDTC in 25 (58%), FTC in 17 (40%), and Hürthle cell carcinoma in 1 (2%). RAS mutation was found in 44% (12/27) and activation of the PI3K pathway in 35% (8/23) of tested tumors. The probability of PFS was 41.7% [95% confidence interval (CI) 7.7-55.5] at 6 months and 20.9% [CI 0-35.7] at 12 months, lower than the 50% expected PFS. At 6 months, 25.6% patients had stable disease, 48.8% were progressive and 25.6% had stopped treatment due to AE. The response to therapy was not influenced by age, sex, histology, or genetic alterations. The overall survivals at 6 and 12 months were 85.9% [CI 76-97] and 78.7 % [CI 67-92], respectively. The mean tumor growth rate decreased from 3.78 mm/month [CI 2.61-4.95] before treatment to 0.8 mm/month [CI -0.2-1.88] during treatment (p < 0.02). Severe grade 3-4 AEs occurred in 27 patients (63%), including hepatitis (25%), hyperglycemia (21%), mood disorders (12%), and skin toxicity (12%), with favorable outcome after temporary or permanent treatment discontinuation or dose reduction.

Conclusions: Buparlisib did not result in significant efficacy in advanced FTC and PDTC. However, the decrease in tumor growth rate may suggest incomplete inhibition of oncogenic pathways and/or escape mechanisms. This should lead to evaluate combined therapy associating inhibitors of both the PI3K and mitogen-activated protein kinase pathways.
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http://dx.doi.org/10.1089/thy.2017.0663DOI Listing
September 2018

Centralization errors in comparative genomic hybridization array analysis of pituitary tumor samples.

Genes Chromosomes Cancer 2018 06 9;57(6):320-328. Epub 2018 Mar 9.

Univ Lyon, Université Lyon 1, Lyon, France.

Reliable interpretation of comparative genomic hybridization array (aCGH) results requires centralization and normalization of the data. We evaluated the reliability of aCGH centralization by comparing aCGH results (with classical centralization-normalization steps) to fluorescence in situ hybridization (FISH) results. In addition, we propose a method to correct centralization bias. Sixty-six pituitary tumors were analyzed (Agilent aCGH + SNP 4 × 180K microarray). For each tumor, the FISH-based log (ratios) of a subset of chromosomes were compared with the corresponding aCGH raw log (ratios). With our new normalization-centralization process, this difference was added to all log (ratios), before performing loess regression on non-altered probes only. Finally, the mean log (ratio) and the percentage of normal probes were compared between CGHnormaliter and our new FISH-based method. For 11 tumors, FISH results and raw CGH log (ratios) differed significantly. In addition, nine tumors showed discrepancies between results generated by CGHnormaliter and our new-method. Such discrepancies seemed to occur with tumours with many abnormalities (0%-40% normal probes), rather than in those tumours with fewer abnormalities (31%-100% normal probes). Five tumors had too few normal probes to allow normalization. In these tumors, which can exhibit many changes in DNA copy number, we found that centralization bias was frequent and uncorrected by current normalization methods. Therefore, an external control for centralization, such as FISH analysis, is required to insure reliable interpretation of aCGH data.
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http://dx.doi.org/10.1002/gcc.22534DOI Listing
June 2018

Predicting thyroid nodule malignancy at several prevalence values with a combined Bethesda-molecular test.

Transl Res 2017 10 22;188:58-66.e1. Epub 2017 Jul 22.

Université Lyon 1, Lyon, France; Service de Biostatistique, Hospices Civils de Lyon, Lyon, France; CNRS UMR5558, Laboratoire de Biométrie et Biologie Évolutive, Équipe Biostatistique-Santé, Villeurbanne, France.

Investigation of thyroid nodules using fine-needle aspiration cytology (FNAC) gives indeterminate results in up to 30% of samples using the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). We present a combined Bethesda-molecular predictor of nodule malignancy to improve the accuracy of the preoperative diagnosis of thyroid nodules. To detect a molecular signature of thyroid nodule malignancy, a molecular test was performed on FNACs from 128 thyroid nodules from prospectively included patients, collected in a tertiary center. The test relied on a transcriptomic array of 20 genes selected from a previous study. An optimal set of seven genes was identified using a logistic regression model. Comparison between the combined predictor (TBSRTC + molecular) and TBSRTC alone used the area under the ROC curve (AUC). Performance of the combined predictor was calculated according to various malignancy prevalence values and benefit-to-harm ratios (B/Hr) (favoring sensitivity or specificity). In our population (36% malignancy prevalence) and with a B/Hr of 1, the combined predictor achieved 95% specificity and 76% sensitivity. The AUC was 93.5%; higher than that of TBSRTC (P = 0.004). Among indeterminate nodules (30% malignancy prevalence), sensitivity and specificity were 52.2% and 96.2%, respectively, with a B/Hr of 1, or 95.7% and 64.2% with a B/Hr of 4 (favoring sensitivity), allowing avoidance of 64% of unnecessary surgeries at the cost of only one false-positive result. In conclusion, this predictor could improve the detection of thyroid nodule malignancy, taking into account malignancy prevalence and B/Hr, and reduce the number of unnecessary thyroidectomies.
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http://dx.doi.org/10.1016/j.trsl.2017.07.005DOI Listing
October 2017

Temozolomide treatment can improve overall survival in aggressive pituitary tumors and pituitary carcinomas.

Eur J Endocrinol 2017 Jun;176(6):769-777

Fédération d'EndocrinologieGroupement Hospitalier Est, Hospices Civils de Lyon, Bron, France.

Objectives: Only few retrospective studies have reported an efficacy rate of temozolomide (TMZ) in pituitary tumors (PT), all around 50%. However, the long-term survival of treated patients is rarely evaluated. We therefore aimed to describe the use of TMZ on PT in clinical practice and evaluate the long-term survival.

Design: Multicenter retrospective study by members of the French Society of Endocrinology.

Methods: Forty-three patients (14 women) treated with TMZ between 2006 and 2016 were included. Most tumors were corticotroph ( = 23) or lactotroph ( = 13), and 14 were carcinomas. Clinical/pathological characteristics of PT, as well as data from treatment evaluation and from the last follow-up were recorded. A partial response was considered as a decrease in the maximal tumor diameter by more than 30% and/or in the hormonal rate by more than 50% at the end of treatment.

Results: The median treatment duration was 6.5 cycles (range 2-24), using a standard regimen for most and combined radiotherapy for six. Twenty-two patients (51.2%) were considered as responders. Silent tumor at diagnosis was associated with a poor response. The median follow-up after the end of treatment was 16 months (0-72). Overall survival was significantly higher among responders ( = 0.002); however, ten patients relapsed 5 months (0-57) after the end of TMZ treatment, five in whom TMZ was reinitiated without success.

Discussion: Patients in our series showed a 51.2% response rate to TMZ, with an improved survival among responders despite frequent relapses. Our study highlights the high variability and lack of standardization of treatment protocols.
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http://dx.doi.org/10.1530/EJE-16-0979DOI Listing
June 2017

Therapeutic innovations in endocrine diseases - part 3 : temozolomide and future therapeutics for aggressive pituitary tumors and carcinomas.

Presse Med 2016 Jun 27;45(6 Pt 2):e211-6. Epub 2016 May 27.

Hospices civils de Lyon, fédération d'endocrinologie, groupement hospitalier Est, 59, boulevard Pinel, 69677 Lyon, France; Université Lyon 1, 69372 Lyon, France; Cancer center of Lyon, Inserm U1052, CNRS UMR5286, signaling, metabolism and tumor progression, 69372 Lyon, France. Electronic address:

Pituitary tumors are the most frequent intracranial tumor and classically considered as benign. However, clinical evidence and recent advances in pathological and molecular analyses suggest that these tumors should be considered as more than a simple endocrine disorder. Descriptions of aggressive pituitary tumors and pituitary carcinomas have increased notably over the last decade following the first report on the successful treatment of pituitary carcinomas using temozolomide. This alkylating agent, widely used to treat glioblastoma, is now the first-line treatment for pituitary tumors resistant to conventional therapies. However, only 40 to 50% of pituitary tumors are sensitive to this treatment. Here, we review results of temozolomide treatment in this indication and discuss the interest of different prognostic markers and perspectives for new therapeutics.
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http://dx.doi.org/10.1016/j.lpm.2016.05.008DOI Listing
June 2016

Pituitary siderosis: the dark side of the pituitary.

Lancet Diabetes Endocrinol 2016 Apr 20;4(4):374. Epub 2015 Nov 20.

Fédération d'Endocrinologie, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France; Université de Lyon, Université Lyon 1, Lyon, France; Neuro-oncology & Neuro-inflammation team, Lyon Neuroscience Research Center, Centre National de la Recherche Scientifique (CNRS) UMR5292, Institut National de la Santé et de la Recherche Médicale (INSERM) U1028, Lyon, France. Electronic address:

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http://dx.doi.org/10.1016/S2213-8587(15)00458-1DOI Listing
April 2016