Publications by authors named "Céline Mouly"

10 Publications

  • Page 1 of 1

IGF-I variability over repeated measures in patients with acromegaly under long-acting somatostatin receptor ligands.

J Clin Endocrinol Metab 2022 Jul 1. Epub 2022 Jul 1.

Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d'Endocrinologie et des Maladies de la Reproduction, Le Kremlin-Bicêtre, France.

Context: In patients with acromegaly on long-term treatment with long-acting somatostatin receptor ligands (SRLs), the time of blood collection for IGF-I measurement after injection is not well defined.

Aim: To assess serum IGF-I dynamics and variability in SRL-treated patients compared with surgically cured patients and healthy controls.

Patients And Methods: Thirty patients under SRLs considered controlled based on a normal previous IGF-I level, ten patients cured by pituitary surgery, and seven healthy subjects underwent four IGF-I weekly determinations.

Results: In SRL-treated patients, the IGF-I SDS (mean±SD) was higher just before injection (0.34±0.66) than at Day 7 (-0.33±0.61; p=0.0041) and Day 14 (-0.23±0.60; p=0.047) after injection, but it did not significantly vary in cured patients and healthy controls. The IGF-I CV was higher in SRL-treated patients than in cured patients or healthy controls (14.4±7.6% vs. 7.9±4.4% and 8.3±3.2%, respectively; p<0.05 for both). Among SRL-treated patients, IGF-I CV was higher in "nonoptimally controlled patients"-i.e., patients with at least one elevated IGF-I value out of four (n=9) compared with "optimally controlled" patients for whom all four IGF-I SDS values were <2.0 (21.3±9.3 vs. 11.6±6.0%; p=0.0019). The latter did not differ from surgically cured patients and healthy controls. The measurement at the farthest distance from the SRL injection was the most predictive of patients with nonoptimally controlled disease.

Conclusions: In patients treated with long-acting SRLs, IGF-I sampling at the farthest distance from SRL injection is the most informative and best predictor of optimal disease control.
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http://dx.doi.org/10.1210/clinem/dgac385DOI Listing
July 2022

High-risk abdominal pediatric paraganglioma.

Pediatr Blood Cancer 2022 Jun 22:e29834. Epub 2022 Jun 22.

Department of Radiation Oncology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.

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http://dx.doi.org/10.1002/pbc.29834DOI Listing
June 2022

First-generation somatostatin receptor ligands and pregnancy: lesson from women with acromegaly.

Endocrine 2020 11 30;70(2):396-403. Epub 2020 Jul 30.

Department of Endocrinology and Metabolic Diseases, CHU Larrey, 24 chemin de Pouvourville, TSA 30030, 31059, Toulouse Cedex, France.

Introduction: Few data are available on the risks of first-generation somatostatin receptor ligands (SRLs) during pregnancy in women treated for acromegaly. Current recommendations suggest the withdrawal of treatment at diagnosis of pregnancy. The aims of this literature review were to evaluate the teratogenic effects and the potential impact of SRLs on maternal and fetal outcomes by comparing acromegalic patients treated or not during pregnancy.

Patients And Methods: This study concerns 141 pregnancies in 127 women with acromegaly: 67 pregnancies in 62 women treated with SRLs during pregnancy and 74 pregnancies in 65 women not medically treated during pregnancy. A second analysis was then realized comparing women treated during 1st trimester only (36 pregnancies) and women treated longer (20 pregnancies).

Results: One malformation (ureteral stenosis) was reported in a newborn of a woman treated with SRL during pregnancy. No difference was found concerning maternal outcomes (gestational diabetes, hypertension, headaches, and delivery mode) and fetal outcomes (birth term, height, and weight). These results were also confirmed for the second analysis.

Conclusions: This review of the literature did report one malformation without being able to prove a specific link with the first-generation SRL treatment. No significant impact on maternal and fetal outcomes is related to first-generation SRL treatment in women with acromegaly. The number of pregnancies is still low and more data are necessary to conclude on the total safety of this treatment during gestation. In the meantime, based on the nonthreatening data from this review of literature, SRL treatment can be continued and/or reintroduced during pregnancy if necessary (mainly for persistent headaches) in women with acromegaly.
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http://dx.doi.org/10.1007/s12020-020-02430-1DOI Listing
November 2020

Germinal defects of SDHx genes in patients with isolated pituitary adenoma.

Eur J Endocrinol 2020 Oct;183(4):369-379

Aix Marseille Univ, APHM, INSERM, MMG, Hospital La Conception, Laboratory of Molecular Biology, Marseille, France.

Background: The '3PAs' syndrome, associating pituitary adenoma (PA) and pheochromocytoma/paraganglioma (PPGL), is sometimes associated with mutations in PPGL-predisposing genes, such as SDHx or MAX. In '3PAs' syndrome, PAs can occur before PPGL, suggesting a new gateway into SDHx/MAX-related diseases.

Objective: To determine the SDHx/MAX mutation prevalence in patients with isolated PAs and characterize PAs of patients with SDHx/MAX mutations.

Design: Genes involved in PAs (AIP/MEN1/CDKN1B) or PPGLs (SDHx/MAX) were sequenced in patients with isolated PAs. We then conducted a review of cases of PA in the setting of '3PAs' syndrome.

Results: A total of 263 patients were recruited. Seven (likely) pathogenic variants were found in AIP, two in MEN1, two in SDHA, and one in SDHC. The prevalence of SDHx mutations reached 1.1% (3/263). Of 31 reported patients with PAs harboring SDHx/MAX mutations (28 published cases and 3 cases reported here), 6/31 (19%) developed PA before PPGL and 8/31 (26%) had isolated PA. The age of onset was later than in patients with AIP/MEN1 mutations. PAs were mainly macroprolactinomas and showed intracytoplasmic vacuoles seen on histopathology.

Conclusions: We discovered SDHx mutations in patients bearing PA who had no familial or personal history of PPGL. However, the question of incidental association remains unresolved and data to determine the benefit of SDHx/MAX screening in these patients are lacking. We recommend that patients with isolated PA should be carefully examined for a family history of PPGLs. A family history of PPGL, as well as the presence of intracytoplasmic vacuoles in PA, requires SDHx/MAX genetic testing of patients.
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http://dx.doi.org/10.1530/EJE-20-0054DOI Listing
October 2020

Clinical characteristics of familial hypocalciuric hypercalcaemia type 1: A multicentre study of 77 adult patients.

Clin Endocrinol (Oxf) 2020 09 14;93(3):248-260. Epub 2020 May 14.

Department of Endocrinology, Larrey Hospital, CardioMet Institute, University Hospital Centre of Toulouse, Toulouse, France.

Objective: Familial hypocalciuric hypercalcaemia type 1 (FHH1), related to heterozygous loss-of-function mutations of the calcium-sensing receptor gene, is the main differential diagnosis for primary hyperparathyroidism. The aim of our study was to describe clinical characteristics of adult patients living in France with a genetically confirmed FHH1.

Design And Patients: This observational, retrospective, multicentre study included 77 adults, followed up in 32 clinical departments in France, with a genetic FHH1 diagnosis between 2001 and 2012.

Results: Hypercalcaemia was diagnosed at a median age of 53 years [IQR: 38-61]. The diagnosis was made after clinical manifestations, routine analysis or familial screening in 56, 34 and 10% of cases, respectively, (n = 58; data not available for 19 patients). Chondrocalcinosis was present in 11/51 patients (22%), bone fractures in 8/56 (14%) and renal colic in 6/55 (11%). The median serum calcium was 2.74 mmol/L [IQR: 2.63-2.86 mmol/L], the median plasma parathyroid hormone level was 4.9 pmol/L [3.1-7.1], and the median 24-hour urinary calcium excretion was 2.8 mmol/24 hours [IQR: 1.9-4.0]. Osteoporosis (dual X-ray absorptiometry) or kidney stones (renal ultrasonography) were found in 6/38 patients (16%) and 9/32 patients (28%), respectively. Fourteen patients (18%) underwent parathyroid surgery; parathyroid adenoma was found in three patients (21%) and parathyroid hyperplasia in nine patients (64%). No correlation between genotype and phenotype was established.

Conclusion: This large cohort study demonstrates that FHH1 clinical characteristics can be atypical in 33 patients (43%). Clinicians should be aware of this rare differential diagnosis in order to adopt an appropriate treatment strategy.
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http://dx.doi.org/10.1111/cen.14211DOI Listing
September 2020

Weight-loss with activation of brown fat: Suspect pheochromocytoma.

Ann Endocrinol (Paris) 2019 Nov 26;80(5-6):314-318. Epub 2019 Jul 26.

Service d'endocrinologie et maladies métaboliques, hôpital Larrey, 24, chemin de Pouvourville, 31059 Toulouse cedex 9, France; Institut Cardiomet, hôpital Rangueil, 1, avenue du Professeur-Jean-Poulhès, 31400 Toulouse, France. Electronic address:

Introduction: Excess catecholamine stimulates heat production in brown adipose tissue (BAT). Activation of BAT can be detected in patients presenting pheochromocytoma.

Case Study: A 58-year-old female patient sought medical advice due to 13 kg weight loss over 2 years accompanied by sweating and high blood pressure. Thoracic-abdominal-pelvic CT-scan revealed a solid 40 mm mass in the left adrenal compartment with peri-adrenal nodules and a solid 80 mm mass at the lower end of the right kidney. FDG-PET scan exhibited intense uptake in the supraclavicular, intercostal, mediastinal, peri-renal, mesenteric, iliac and inguinal spaces. Renal tumor with locoregional infiltration and remote metastases was initially considered. Diagnosis of pheochromocytoma was subsequently confirmed by a 10-fold increase in urinary catecholamine, metanephrine and normetanephrine levels. Left adrenalectomy confirmed the diagnosis of pheochromocytoma, with 3 lymph-node metastases in the adjacent adipose tissue surrounded by brown fat. The patient was clinically asymptomatic with normal blood pressure at 3 months post-surgery. A weight gain of 6 kg was recorded, with normalisation of catecholamines/metanephrine/normetanephrine levels. Bilateral peri-renal infiltration (including the right renal mass) disappeared on CT-scan, and TEP-18-FDG no longer showed hypermetabolism. Recurrent mediastinal metastases were diagnosed 6 months after surgery.

Conclusion: Brown fat activation may mislead diagnosis of pheochromocytoma, suggesting multi-metastatic extra-adrenal tumor, if clinicians are not aware of it.
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http://dx.doi.org/10.1016/j.ando.2019.06.004DOI Listing
November 2019

Gestational diabetes and acromegaly: Single-centre experience of 14 pregnancies.

Clin Endocrinol (Oxf) 2019 12 14;91(6):805-809. Epub 2019 Oct 14.

Service d'Endocrinologie, Maladies métaboliques et Nutrition, Pôle Cardio-Vasculaire et Métabolique, CHU Larrey, Toulouse, France.

Introduction: The prevalence of gestational diabetes (GD) in women with acromegaly is rarely reported. The aims of this study were to evaluate the prevalence of GD in acromegalic women submitted to a systematic screening for GD and then to compare women with or without GD.

Patients And Methods: We studied 14 pregnancies in 11 women (34.0 ± 3.6 years) treated with somatostatin analogues after a pituitary surgery (n = 6) or as primary (n = 5) therapy, and treatment was discontinued at the time of pregnancy diagnosis for 13 pregnancies. One woman was diagnosed with acromegaly during pregnancy and was treated with octreotide LAR between 12 and 18 weeks of gestation. Before pregnancy, no women had diabetes mellitus, and GH/IGF-1 hypersecretion was uncontrolled in 6 women.

Results: Gestational diabetes was diagnosed during 7 pregnancies (50%) in 6 women (one woman had GD during her 2 pregnancies), according to fasting blood glucose (n = 5) or to an oral glucose tolerance test (n = 2). Before pregnancy, IGF-1 was not controlled in 4 GD+ and in 2 GD- women. Women with GD were not significantly older and had increased pregestational BMI (P = .02), with a more frequent family history of type 2 diabetes, no personal history of GD but of macrosomia for one patient.

Conclusion: The prevalence of GD in our women is higher than that reported in the literature, probably resulting from the systematic GD screening and to the age of women. Therefore, routine screening of GD should be considered in women with acromegaly, particularly in those with risk factors for GD and with uncontrolled IGF-1 levels before pregnancy.
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http://dx.doi.org/10.1111/cen.14097DOI Listing
December 2019

Incidence of thyroid dysfunctions during treatment with nivolumab for non-small cell lung cancer: Retrospective study of 105 patients.

Presse Med 2019 Apr 17;48(4):e199-e207. Epub 2019 Apr 17.

CHU Larrey, Department of endocrinology and metabolic diseases, 31059 Toulouse, France. Electronic address:

Introduction: Immunotherapy is a standard not only in second line but also in first line treatment in patients with non-small cell lung cancer (NSCLC) and other tumors. Thyroid dysfunctions are the most common endocrine toxicities.

Objective: To determine the incidence of thyroid dysfunctions during treatment with a PD-1 monoclonal antibody (nivolumab) in patients with NSCLC.

Methods: Retrospective study of patients treated with nivolumab for NSCLC between May 2015 and December 2016; euthyroidism within the 3 months preceding immunotherapy; monitoring of thyroid function tests until stopping nivolumab, death or February 2017. Patients treated with levothyroxine, amiodarone or another immunotherapy were excluded.

Results: Among 183 patients treated, 105 fullfilled the inclusion criteria (72 males, median age: 61 years [range: 41-80]). Fifteen patients (14.3%) experienced a thyroid dysfunction; among them, compared to the "control" group (n=90), we found more females (53.3% vs. 27.8%; P=0.07), and younger patients (median age: 56 years vs. 62 years; P=0.02). Thirteen patients had thyrotoxicosis (median onset: 8 weeks), and then hypothyroidism was observed in 5 patients. Isolated hypothyroidism was rare (n=2) and late (median: 30 weeks). Three patients had anti-TPO antibodies. Three patients discontinued immunotherapy transiently due to thyroid dysfunctions. After a median follow-up of 9 months [95% CI, 7.5-10.3], one patient (6.7%) in the "thyroid dysfunctions" group and 30 patients (33.3%) in the "control" group died, with a trend toward a higher overall survival in the "thyroid dysfunctions" group (HR: 0.16 [95% CI, 0.02-1.15]; P=0.07).

Conclusion: Thyroid dysfunctions (isolated thyrotoxicosis, biphasic thyroiditis and hypothyroidism) were common, and required patients with NSCLC to be screened during nivolumab therapy.
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http://dx.doi.org/10.1016/j.lpm.2018.10.019DOI Listing
April 2019

Medical therapy in patients with endogenous hypoglycaemia: Is euglycaemia achievable?

Clin Endocrinol (Oxf) 2019 06 25;90(6):798-804. Epub 2019 Mar 25.

Service d'Endocrinologie, Maladies Métaboliques et Nutrition et Institut CardioMet, Centre Hospitalier Universitaire Rangueil-Larrey, Toulouse, France.

Context: While the only curative treatment for patients with endogenous hypoglycaemia related to inappropriate insulin or to insulin growth factor 2 (IGF2) secretion is surgery, medical treatment to normalize plasma glucose levels can be useful.

Objective: The aim of this prospective single centre study was to assess whether patients with endogenous hypoglycaemia, considered euglycaemic with medical treatments, experienced asymptomatic hypo- or hyperglycaemic excursions.

Patients And Methods: All patients with endogenous hypoglycaemia related to inappropriate insulin or to IGF2 secretion between 2012 and 2016 and considered normoglycaemic with medical treatment (absence of clinical hypoglycaemia and self-monitoring blood glucose in the normal range) were enroled and underwent a six-day continuous glucose monitoring (CGM) recording.

Results: Twenty-seven patients (inappropriate insulin secretion n = 25 and IGF2 secretion n = 2), treated with diazoxide (n = 16), somatostatin analogues (n = 7), glucocorticoids (n = 3) or a combination of these treatments (n = 1) were enroled. Twenty-five CGMs were analysed. CGM confirmed normoglycaemia in 11/25 patients (44%). Hypoglycaemias below 0.60 g/L were present in seven patients (28%) and were associated with hyperglycaemic excursions above 1.40 g/L in five patients. Seven patients (28%) had only hyperglycaemic excursions. Based on these results, treatment was modified in 14 patients (56%).

Conclusion: Despite the disappearance of hypoglycaemia-related clinical symptoms and normalization of blood glucose self-monitoring data, 56% of the patients with endogenous hypoglycaemia treated with medical therapy experienced asymptomatic hypo- and/or hyperglycaemia. Continuous glucose monitoring could be a useful approach to reveal and prevent hypo- or hyperglycaemic excursions.
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http://dx.doi.org/10.1111/cen.13961DOI Listing
June 2019

Severe Inflammatory Ophthalmopathy in a Euthyroid Patient during Nivolumab Treatment.

Eur Thyroid J 2018 Mar 4;7(2):84-87. Epub 2018 Jan 4.

Department of Endocrinology and Metabolic Diseases, Larrey University Hospital, Toulouse, France.

Introduction: Nivolumab is a promising treatment in patients with advanced malignancies. Among immune-related adverse events, autoimmune thyroid disorders are frequently reported.

Patient: A 61-year-old male patient had no history of familial or personal thyroid disease. In 2012, this patient, a heavy smoker, presented with non-small-cell lung cancer that was treated with radiotherapy and chemotherapy. In 2015, the cancer progressed with cervical compressive symptoms, and the patient was treated with nivolumab.

Results: After 3 infusions, bilateral eyelid ptosis and bilateral conjunctival redness with chemosis were observed. Ophthalmologic examination revealed severe proptosis with complete ophthalmoplegia but with normal vision, color test, and optic disk. Thyroid function tests were normal (TSH = 0.65 mU/L, free T = 15.4 pmol/L) without anti-thyroperoxidase or anti-TSH receptor antibodies. CT scan of the orbits confirmed marked bilateral proptosis with expansion of the orbital adipose tissue without significant thickening of extraocular muscles. T2-weighted MRI showed inflammation of orbital adipose tissue. Nivolumab treatment was withdrawn, and the patient received weekly intravenous high-dose methylprednisolone (1 g for 2 weeks, 500 mg for 4 weeks, and 250 mg for 5 weeks). After the first 3 cycles, significant improvement of left chemosis was observed whereas bilateral ptosis and ophthalmoplegia were unchanged. The patient was euthyroid without thyroid autoimmunity 1 week prior to his death due to massive hemoptysis.

Conclusion: We report severe inflammatory ophthalmopathy in a euthyroid patient with non-small-cell lung cancer during nivolumab therapy. The occurrence of such ophthalmic adverse events is likely to increase during nivolumab therapy in patients with advanced malignancies.
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http://dx.doi.org/10.1159/000485742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869363PMC
March 2018
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