Sunitinib for metastatic progressive phaeochromocytomas and paragangliomas: results from FIRSTMAPPP, an academic, multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial.

BACKGROUND: No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas. METHODS: FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment. FINDINGS: From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock. INTERPRETATION: This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas. FUNDING: French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.

Outcome on Mesenteric Mass Response of Small-Intestinal Neuroendocrine Tumors Treated by 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy: The MesenLuth Study, a National Study from the French Group of Endocrine Tumors and Endocan-RENATEN Network.

A mesenteric mass (MM), characterized by fibrotic reaction, is present in most small-intestinal neuroendocrine tumors (SI-NETs). 177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) has shown its efficacy in patients with progressive SI-NETs. However, because of specific tissue characteristics of desmoplastic MMs, we hypothesize that these lesions may be refractory to 177Lu-DOTATATE PRRT. Methods: From the national French Groupe d'étude des Tumeurs Endocrines database, we identified patients with an advanced SI-NET and a MM (≥2 cm with a retractile aspect) of a SI-NET treated by at least 1 course of 177Lu-DOTATATE PRRT. The primary endpoint was a MM objective response rate (ORR) of less than 5%. Secondary endpoints were metabolic response, MM-related safety, and clinical response, as well as MM progression-free survival (PFS) and non-MM PFS. Results: In total, 52 patients were included. The MM ORR was 4% (n = 2), and the non-MM ORR was 8% (n = 4). No patient had a MM metabolic response, and the non-MM metabolic response rate was 12% (n = 6). Among the 26 patients with baseline MM-related symptoms, 46% had a clinical response. Four patients presented with gastrointestinal complications during PRRT. The median MM-related PFS was not reached, and the non-MM PFS was 50.3 mo (95% CI, 38.2-61.7 mo). Conclusion: This study confirms that 177Lu-DOTATATE PRRT does not lead to morphologic response on MMs (ORR < 5%). However, it allows MM stability, with few MM-related side effects, and has a relevant impact on MM-related symptoms.

Performance of [18F]fluorocholine PET/CT in MEN1-related primary hyperparathyroidism before initial surgery or for persistent/recurrent disease.

PURPOSE: The aims of the study were to evaluate the performance and robustness of [18F]fluorocholine PET/CT in detecting hyperfunctioning parathyroid glands in MEN1-related primary hyperparathyroidism (pHPT) at different stages of their disease. METHODS: Retrospective French multicenter study including patients with MEN1 pHPT who underwent [18F]fluorocholine PET/CT at initial diagnosis or for evaluation of persistent/recurrent disease. PET/CT were independently reviewed by two readers in a blinded manner. The assessment of PET/CT on a per-patient basis was assessed using a comprehensive set of criteria that considered pathological findings or agreement with alternative diagnostic methods in non-operated patients. The secondary objectives included the analysis of the performance of PET/CT at a per-lesion level, with reference to a pathological Gold Standard, and examining its interobserver reproducibility. RESULTS: A total of 71 MEN1 patients were included (73 PET/CT) in the study. At the per-patient level (entire cohort), [18F]fluorocholine PET/CT sensitivity ranged from 98.5 to 100% among the different readers. An average of 1.77 glands per PET was described, with 2.35 glands at the initial diagnosis (n = 23) and 1.5 in previously operated cases (n = 50). PET/CT detected more lesions than conventional imaging work-up (neck ultrasound and/or scintigraphy). At the per-lesion level (41 operated patients), sensitivity ranged across different readers from 84.4 to 87%, and specificity ranged from 94.7 to 98.8%. At initial diagnosis, all patients that exhibited 3 or more abnormal glands on PET underwent subtotal parathyroidectomy while 7 out of 13 patients with 1 or 2 gland abnormalities on PET underwent less than subtotal parathyroidectomy. Finally, the degree of inter-observer agreement was high. CONCLUSION: [18F]fluorocholine PET/CT is a reliable and robust imaging modality for the evaluation of MEN1-related pHPT and could guide surgeons in achieving the optimal benefit-risk ratio. This study gives a great impetus for its adoption as a primary diagnostic tool in this context.

Adjuvant mitotane versus surveillance in low-grade, localised adrenocortical carcinoma (ADIUVO): an international, multicentre, open-label, randomised, phase 3 trial and observational study.

BACKGROUND: Adjuvant treatment with mitotane is commonly used after resection of adrenocortical carcinoma; however, treatment remains controversial, particularly if risk of recurrence is not high. We aimed to assess the efficacy and safety of adjuvant mitotane compared with surveillance alone following complete tumour resection in patients with adrenocortical carcinoma considered to be at low to intermediate risk of recurrence. METHODS: ADIUVO was a multicentre, open-label, parallel, randomised, phase 3 trial done in 23 centres across seven countries. Patients aged 18 years or older with adrenocortical carcinoma and low to intermediate risk of recurrence (R0, stage I-III, and Ki67 ≤10%) were randomly assigned to adjuvant oral mitotane two or three times daily (the dose was adjusted by the local investigator with the target of reaching and maintaining plasma mitotane concentrations of 14-20 mg/L) for 2 years or surveillance alone. All consecutive patients at 14 study centres fulfilling the eligibility criteria of the ADIUVO trial who refused randomisation and agreed on data collection via the European Network for the Study of Adrenal Tumors adrenocortical carcinoma registry were included prospectively in the ADIUVO Observational study. The primary endpoint was recurrence-free survival, defined as the time from randomisation to the first radiological evidence of recurrence or death from any cause (whichever occurred first), assessed in all randomly assigned patients by intention to treat. Overall survival, defined as time from the date of randomisation to the date of death from any cause, was a secondary endpoint analysed by intention to treat in all randomly assigned patients. Safety was assessed in all patients who adhered to the assigned regimen, which was defined by taking at least one tablet of mitotane in the mitotane group and no mitotane at all in the surveillance group. The ADIUVO trial is registered with ClinicalTrials.gov, NCT00777244, and is now complete. FINDINGS: Between Oct 23, 2008, and Dec 27, 2018, 45 patients were randomly assigned to mitotane and 46 to surveillance alone. Because the study was discontinued prematurely, 5-year recurrence-free and overall survival are reported instead of recurrence-free and overall survival as defined in the protocol. 5-year recurrence-free survival was 79% (95% CI 67-94) in the mitotane group and 75% (63-90) in the surveillance group (hazard ratio 0·74 [95% CI 0·30-1·85]). Two people in the mitotane group and five people in the surveillance group died, and 5-year overall survival was not significantly different (95% [95% CI 89-100] in the mitotane group and 86% [74-100] in the surveillance group). All 42 patients who received mitotane had adverse events, and eight (19%) discontinued treatment. There were no grade 4 adverse events or treatment-related deaths. INTERPRETATION: Adjuvant mitotane might not be indicated in patients with low-grade, localised adrenocortical carcinoma considering the relatively good prognosis of these patients, and no significant improvement in recurrence-free survival and treatment-associated toxicity in the mitotane group. However, the study was discontinued prematurely due to slow recruitment and cannot rule out an efficacy of treatment. FUNDING: AIFA, ENSAT Cancer Health F2-2010-259735 programme, Deutsche Forschungsgemeinschaft, Cancer Research UK, and the French Ministry of Health.

Surgery of primary lung carcinoid tumors at metastatic stage: A national study from the French Group of Endocrine Tumors (GTE) and ENDOCAN-RENATEN network.

The outcome following surgery for patients with primary lung neuroendocrine tumors at metastatic stage remains poorly characterized. We conducted a retrospective national study including patients with metastatic lung neuroendocrine tumors at diagnosis. We performed a safety study to evaluate major morbidity and mortality of surgical resection of the primary tumor and compared patients in the operative to the nonoperative group. A total of 155 patients were included: 41 in the operative group and 114 in the nonoperative group, median age was 64 years. Metastases were mainly located in the liver (74.2%) and the bone (49.7%). The primary endpoint was met as the rate of major complications was 4.9% and there was no postoperative mortality. In the operative group 42.5% of patients had improvement of their pulmonary symptoms versus 14.4% in the nonoperative group. The median overall survival was not reached in the operative group and was 4.3 years (95% CI [3.5;4.9]) in the nonoperative group (univariate analysis, HR = 0.42 95% CI [0.23-0.77], p = .002). After multivariate analysis, only an ECOG-PS ≥1 (vs. 0, HR = 2.44, 95% CI [1.46;4.07], p = .001) and >1 metastatic site (vs. 1; HR = 1.83, 95% CI [1.06;3.16], p = .030) remained significantly associated with overall survival. The resection of the primary tumor was not significantly associated with overall survival (HR = 0.63, 95% CI [0.32;1.24], p = .183). In conclusion, surgery of primary lung neuroendocrine tumors at metastatic stage is a safe option that should be considered in selected patients in order to improve symptoms with a view to improving their quality of life. Larger studies are warranted to evaluate the impact of surgery on survival.

[French recommendations for malignant pheochromocytomas and paragangliomas by the national ENDOCAN-COMETE network]. / Recommandations du réseau national ENDOCAN-COMETE pour la prise en charge des phéochromocytomes et paragangliomes métastatiques.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors, developed respectively in the adrenal medulla and in extra-adrenal locations. Their malignancy is defined by the presence of distant metastases. Forty percent of them are inherited and can be part of different hereditary syndromes. Their management is ensured in France by the multidisciplinary expert centers of the ENDOCAN-COMETE national network "Cancers of the Adrenal gland", certified by the National Cancer Institute and discussed within multidisciplinary team meetings. The diagnostic and therapeutic work-up must be standardized, based on an expert analysis of clinical symptoms, hormonal biological secretions, genetics, morphological and specific metabolic imaging. In the context of a heterogeneous survival sometimes beyond seven to ten years, therapeutic intervention must be justified. This is multidisciplinary and relies on surgery, interventional radiology, external or internal radiotherapy and medical treatments such as sunitinib or dacarbazine and temodal chemotherapy. The personalized approach based on functional imaging fixation status and genetics is progressing despite the extreme rarity of this disease.

Risk factors for intraoperative complications, postoperative complications, and prolonged length of stay after laparoscopic adrenalectomy by transperitoneal lateral approach: a retrospective cohort study of 547 procedures.

BACKGROUND: Laparoscopic adrenalectomy (LA) is the gold standard for the resection of most adrenal lesions. A precise delineation of factors influencing its outcomes is lacking. The aim of this study was to assess factors associated with intraoperative complications, postoperative complications, and prolonged length of stay (LOS) after LA. METHODS: Patients who underwent LA from 1999 to 2021 in a single-academic-institution were included. Patient and disease-specific data, intraoperative complications, postoperative complications according to Dindo-Clavien (DC) scale, and LOS were recorded. Predictive factors of complications and prolonged LOS were determined by logistic regression. RESULTS: We identified 530 patients who underwent 547 LA. Intraoperative complications occurred in 33 patients (6.0%). Postoperative complications ≥  DC grade 2 occurred in 73 patients (13.35%); severe postoperative complications ≥ DC grade 3 in 14 patients (2.56%). Postoperative complications were positively associated with age ≥ 72 (OR 1.14 [95% CI 1.02-1.29]), intraoperative complications (OR 1.36 [95% CI 1.14-1.63]), and negatively associated with non functional adenomas (OR 0.88 [95% CI 0.7-0.99]), and right adrenalectomy (OR 0.91 [95% CI 0.86-0.97]). Severe postoperative complications were positively associated with chronic obstructive pulmonary disease (COPD, OR 1.08 [95% CI 1.00-1.17]), and negatively associated with right adrenalectomy (OR 0.97 [95% CI 0.92-0.99]). Prolonged LOS was associated with age ≥ 72 (OR 1.21 [95% CI 1.05-1.41]), and COPD (OR 1.20 [95% CI 1.01-1.44]). CONCLUSIONS: LA remains safe when performed by surgeons with expertise. Right adrenalectomy resulted in less postoperative overall and severe complications. The risk-benefit equation should be carefully assessed before left LA in older patients with COPD.

Outcome of adrenocortical carcinoma patients included in early phase clinical trials: Results from the French network ENDOCAN-COMETE.

BACKGROUND: At metastatic stage, treatment of adrenocortical carcinoma (ACC) relies in first line on mitotane therapy, combination of mitotane with locoregional therapies or cisplatin-based chemotherapy according to initial presentation. In second line, ESMO-EURACAN recommendations favour enrolment of patients in clinical trials investigating experimental therapies. However, the benefit of this approach remains unknown. METHODS: The aim of our retrospective study was to analyse the inclusion and outcomes of all patients of the French cohort ENDOCAN-COMETE included in early clinical trials between 2009 and 2019. RESULTS: Of the 141 patients for whom a local or national multidisciplinary tumour board recommended, as first choice, to look for clinical trial, 27 patients (19%) were enroled in 30 early clinical trials. Median progression-free survival (PFS) was 3.02 months (95% confidence interval [95% CI]; 2.3-4.6) and median overall survival (OS) was 10.2 months (95% CI; 7.13-16.3) while the best response, evaluable in 28 of 30 trial participants according to RECIST 1.1 criteria, was partial response for 3 patients (11%) stable disease for 14 patients (50%) and progressive disease for 11 patients (39%), resulting in a disease control rate of 61%. Median growth modulation index (GMI) in our cohort was 1.32, with a significantly prolonged PFS in 52% of the patients compared to the previous line. The Royal Marsden Hospital (RMH) prognostic score was not associated with OS in this cohort. CONCLUSION: Our study suggests that patients with metastatic ACC benefit from inclusion in early clinical trials in second line. As recommended, if a clinical trial is available, it should be the first choice for suitable patients.

[Guidelines of the French National ENDOCAN-COMETE, Association of Endocrine Surgery, Society of Urology for the management of adrenocortical carcinoma]. / Recommandations conjointes du réseau National ENDOCAN-COMETE, de l'Association francophone de chirurgie endocrinienne et de la Société française d'urologie pour la prise en charge du carcinome corticosurrénalien.

The adrenocortical carcinoma (ACC) is a primary malignant tumor developed from the adrenal cortex, defined by a Weiss score≥3. Its prognosis is poor and depends mainly on the stage of the disease at diagnosis. Care is organized in France by the multidisciplinary expert centers of the national ENDOCAN-COMETE "Adrenal Cancers" network, certified by the National Cancer Institute. This document updates the guidelines for the management of ACC in adults based on the most robust data in the literature. It's divided into 11 chapters: (1) circumstances of discovery; (2) pre-therapeutic assessment; (3) diagnosis of ACC; (4) oncogenetics; (5) prognostic classifications; (6) treatment of hormonal hypersecretion; (7) treatment of localized forms; (8) treatment of relapses; (9) treatment of advanced forms; (10) follow-up; (11) the particular case of ACC and pregnancy. R0 resection of all localized ACC remains an unmet need and it must be performed in expert centers. Flow-charts for the therapeutic management of localized ACC, relapse or advanced ACC are provided. It was written by the experts from the national ENDOCAN-COMETE network and validated by all French Societies involved in the management of these patients (endocrinology, medical oncology, endocrine surgery, urology, pathology, genetics, nuclear medicine, radiology, interventional radiology).

Immunohistochemical characterization of a steroid-secreting oncocytic adrenal carcinoma responsible for paraneoplastic hyperparathyroidism.

We report a unique case of a 44-year-old man with paraneoplastic hyperparathyroidism due to an oncocytic adrenocortical carcinoma (stage pT3N0R0M0, ENSAT 2 with a 4% Ki-67). Paraneoplastic hyperparathyroidism was associated with mild adrenocorticotropic hormone (ACTH)-independent hypercortisolism and increased estradiol secretion responsible for gynecomastia and hypogonadism. Biological investigations performed in blood samples from peripheral and adrenal veins revealed that the tumor secreted parathyroid hormone (PTH) and estradiol. Ectopic PTH secretion was confirmed by abnormally high expression of PTH mRNA and clusters of PTH immunoreactive cells in the tumor tissue. Double-immunochemistry studies and analysis of contiguous slides for the expression of PTH and steroidogenic markers (scavenger receptor class B type 1 [SRB1], 3ß-hydroxysteroid dehydrogenase [3ß-HSD], and aromatase) were performed. The results suggested the presence of two tumor cells subtypes with large cells with voluminous nuclei producing only PTH and that were distinct from steroid-producing cells.

Dual-tracer 99mTc-sestamibi/ 123I imaging in primary hyperparathyroidism.

Surgery is the only curative treatment for primary hyperparathyroidism (PHPT). Preoperative imaging is always recommended. 99mTc-sestamibi scintigraphy is often used in combination with neck ultrasonography as first-line imaging. 99mTc-sestamibi scintigraphy plays a major role in depicting ectopic parathyroid lesions, as well as in guiding a targeted, minimally invasive parathyroidectomy (MIP). Detecting multiple gland disease (MGD) is important to reduce the risks of surgical failure or unplanned conversion to bilateral surgery. However, the ability to recognize MGD varies greatly depending on the 99mTc-sestamibi imaging protocol that is used. Dual-tracer 99mTc-sestamibi/123I highly improves MGD detection compared to single-tracer "dual-phase" 99mTc-sestamibi imaging. It can thus improve patient selection for MIP. The main requirements for successful dual-tracer imaging are: 1) to acquire 99mTc-sestamibi and 123-iodine images simultaneously, thus avoiding motion artifacts on subtraction images; to use neck pinhole imaging, in addition to planar imaging, to improve resolution and MGD detection; to follow with dual-tracer SPECT/CT imaging to better define anatomic position of detected parathyroid lesions. If dual-tracer 99mTc-sestamibi/123I and neck ultrasonography are negative or inconclusive, the second-line imaging in our practice is 18F-fluorocholine PET/CT. The CT component of 18F-fluorocholine PET/CT is performed as non-enhanced acquisition plus a contrast-enhanced arterial phase acquisition, to minimize the risk from false-positives due to choline uptake in inflammatory lymph nodes. We use the same strategy of first-line dual-tracer 99mTc-sestamibi/123I plus neck ultrasonography, followed if necessary by second-line contrast-enhanced 18F-fluorocholine PET/CT, in patients requiring reoperation for persistent or recurrent PHPT. Additional localization techniques are now rarely necessary.

Efficacy and Safety of Osilodrostat in Paraneoplastic Cushing Syndrome: A Real-World Multicenter Study in France.

CONTEXT: Prospective studies have demonstrated the efficacy of osilodrostat in Cushing disease. No study has evaluated osilodrostat in a series of patients with paraneoplastic Cushing syndrome/ectopic adrenocorticotropin syndrome (PNCS/EAS). OBJECTIVE: This work aimed to evaluate in France the real-world efficacy and safety of osilodrostat in patients with PNCS/EAS. METHODS: A total of 33 patients with PNCS/EAS with intense/severe hypercortisolism were involved in this retrospective, multicenter, real-world study. Patients received osilodrostat between May 2019 and March 2022 at a median initial dose (range) of 4 mg/day (1-60) and maximum dose, 20 mg/day (4-100), first under patient then cohort temporary authorizations and after marketing authorization. Regimens used titration (n = 6), block and replace (n = 16), or titration followed by block and replace (n = 11). RESULTS: In 11 patients receiving osilodrostat as first-line monotherapy, median 24-hour urinary free cortisol (24h-UFC) decreased dramatically (from 26 × upper limit of normal [ULN; 2.9-659] to 0.11 × ULN [0.08-14.9]; P < .001). In 9 of them, 24h-UFC normalization was achieved in 2 weeks (median). Thirteen additional patients were previously treated with classic steroidogenesis inhibitors but 10 of these 13 were not controlled. In these patients, osilodrostat monotherapy, used as second line, induced a significantly decreased of 24h-UFC (from 2.6 × ULN [1.1-144] to 0.22 × ULN [0.12-0.66]; P < .01). Nine additional patients received osilodrostat in combination with another anticortisolic drug, decreasing 24h-UFC from 11.8 × ULN (0.3-247) to 0.43 × ULN (0.33-2.4) (P < .01). In parallel, major clinical symptoms/comorbidities improved dramatically with improvement in blood pressure, hyperglycemia, and hypokalemia, allowing the discontinuation or dose reduction of patient treatments. Adrenal insufficiency (grade 3-4) was reported in 8 of 33 patients. CONCLUSION: Osilodrostat is a rapidly efficient therapy for PNCS/EAS with severe/intense hypercortisolism. Osilodrostat was generally well tolerated; adrenal insufficiency was the main side effect.

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.

SFE-AFCE-SFMN 2022 Consensus on the management of thyroid nodules: Initial work-up for thyroid nodules.

The SFE-AFCE-SFMN 2022 consensus deals with the management of thyroid nodules, a condition that is a frequent reason for consultation in endocrinology. In more than 90% of cases, patients are euthyroid, with benign non-progressive nodules that do not warrant specific treatment. The clinician's objective is to detect malignant thyroid nodules at risk of recurrence and death, toxic nodules responsible for hyperthyroidism or compressive nodules warranting treatment. The diagnosis and treatment of thyroid nodules requires close collaboration between endocrinologists, nuclear medicine physicians and surgeons, but also involves other specialists. Therefore, this consensus statement was established jointly by 3 societies: the French Society of Endocrinology (SFE), French Association of Endocrine Surgery (AFCE) and French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This section deals with the initial work-up for thyroid nodules in adult patients, including clinical and biological evaluation, standardized ultrasound characterization and EU-TIRADS-based nodule selection for fine-needle aspiration biopsy. Indications for thyroid core-biopsies or open surgical biopsies and for cross-sectional imaging of the neck and upper chest are also mentioned.