[Diagnosis and etiology of primary adrenal insufficiency]. / Diagnostic et étiologie de l'insuffisance surrénalienne primaire.

Since its first description in 1855, our understanding of primary adrenal insufficiency has greatly evolved. However, diagnosis is often delayed, as symptoms are frequently nonspecific in the early stages of the disease. In this article, we review the classical manifestations, associated diseases, as well as the diagnostic algorithm for primary adrenal insufficiency, aiming to enable earlier diagnosis.

Depuis la première description en 1855, nos connaissances de l'insuffisance surrénalienne primaire ont beaucoup évolué. Cependant, le diagnostic est souvent retardé, les symptômes étant fréquemment aspécifiques aux premiers stades de la maladie. Dans cet article, nous rappelons les manifestations classiques, les maladies associées, ainsi que l'algorithme diagnostique de l'insuffisance surrénalienne primaire, afin de permettre un diagnostic plus précoce.

[Weight gain during menopause: physiology and practical implications]. / Prise de poids pendant la ménopause : physiologie et implications pratiques.

Fluctuations in sex hormones at different stages of reproductive life, such as the menopausal transition, have been suggested as players in weight regulation. Indeed, the transition from a predominantly estrogenic state to an androgenic state characteristic of the menopausal transition contributes to changes in body composition with accumulation of fat and simultaneous loss of lean mass. However, whether these changes contribute to the weight gain remains debatable. Other physiological and psychosocial factors come into play. It is therefore important to offer individualized support with the objective to minimize the risk of weight gain and associated complications.

La fluctuation des hormones sexuelles à différentes étapes de la vie reproductive, telles que la transition ménopausique, a été proposée comme une des composantes de la régulation de poids. Effectivement, le passage d'un état principalement œstrogénique à un état androgénique, caractéristique de la transition ménopausique, contribue à des modifications de la composition corporelle avec une accumulation de graisse et une perte simultanée de masse maigre. Cependant, la question de savoir si ces changements contribuent à une prise de poids reste discutable. L'obésité est une maladie multifactorielle et d'autres facteurs d'ordre physiologique et psychosociaux rentrent en jeu. Il est donc important d'offrir un accompagnement individualisé aux femmes concernées pour les aider à minimiser le risque de prise pondérale et des complications associées.

[What's new in endocrinology]. / Endocrinologie : ce qui a changé en 2022.

Thyroid problems are frequent in pregnant women; recent data allow observation only in women with positive antithyroperoxidase antibodies (anti-TPO) but normal thyroïd function. New minimally invasive techniques are being developed for the management of thyroid nodules; radiofrequency ablation is effective for benign nodules. The management of Cushing's syndrome is oriented towards a more personalized approach; new treatments are available, with increased efficacy and a very good safety profile.

Les problématiques thyroïdiennes sont fréquentes chez la femme enceinte, des données récentes permettent cependant une attitude de surveillance chez les femmes avec des anticorps antithyroperoxydase (anti-TPO) positifs mais en euthyroïdie. De nouvelles techniques minimalement invasives pour la prise en charge des nodules thyroïdiens sont développées et la thermoablation par radiofréquence est efficace pour les nodules bénins. La prise en charge du syndrome de Cushing s'oriente vers une approche personnalisée. Des nouveaux traitements sont proposés, avec une efficacité accrue et un très bon profil de sécurité.

[What's new in endocrinology]. / Endocrinologie.

The management of Graves' orbitopathy, an extraocular manifestation of the disease and the main contributor to morbidity, is the subject of new recommendations, published in 2021. The treatment of low risk differentiated thyroid cancer is simplified, with less surgery and less radioiodine treatment and at lower dose. The management of acromegaly is oriented towards a personalized approach; prognostic factors are more widely used, and the treatment of complications is emphasized.

La prise en charge de l'orbitopathie de Basedow, manifestation extraoculaire de la maladie et principal contributeur de morbidité, fait l'objet de nouvelles recommandations, publiées en 2021. Le traitement du cancer thyroïdien bien différencié et à faible risque de récidive connaît une désescalade thérapeutique avec moins de chirurgies et de curiethérapies et à plus faible dose. La prise en charge de l'acromégalie s'oriente vers une approche personnalisée ; des facteurs pronostiques sont proposés et l'accent est mis sur le traitement des complications de la maladie et du traitement subi.

Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD.

Thyroid hormones control lipid metabolism by exhibiting specific effects on the liver and adipose tissue in a coordinated manner. Different diseases of the thyroid gland can result in hypothyroidism. Hypothyroidism is frequently associated with dyslipidemia. Hypothyroidism-associated dyslipidemia subsequently results in intrahepatic accumulation of fat, leading to nonalcoholic fatty liver disease (NAFLD), which leads to the development of hepatic insulin resistance. The prevalence of NAFLD in the western world is increasing, and evidence of its association with hypothyroidism is accumulating. Since hypothyroidism has been identified as a modifiable risk factor of NAFLD and recent data provides evidence that selective thyroid hormone receptor ß (THR-ß) agonists are effective in the treatment of dyslipidemia and NAFLD, interest in potential therapeutic options for NAFLD targeting these receptors is growing. In this review, we summarize current knowledge regarding clinical and molecular data exploring the association of hypothyroidism, dyslipidemia and NAFLD.

[Endocrine care of gender-incongruent persons]. / Prise en charge des personnes avec incongruence de genre : le point de vue de l'endocrinologue.

Health care of gender-incongruent persons deserves optimization. The new World Health Organization ICD-11, introduced this year, classifies gender-incongruence to « conditions related to sexual health ¼, and not anymore to « mental and behavioral disorders ¼. From an endocrine perspective, gender-affirming hormonal treatment induces physical changes consistent with gender identity, but good-quality, long follow-up studies concerning efficacy and safety are needed. Improvements in training of medical professionals as well as a specialized multidisciplinary approach are important measures to be taken.

Les soins médicaux offerts aux personnes avec incongruence de genre méritent d'être optimisés. La nouvelle Classification internationale des maladies, 11e version, de l'OMS, présentée cette année, classe l'incongruence de genre parmi les « conditions liées à la santé sexuelle ¼, et non plus dans les « troubles mentaux et du comportement ¼. Sur le plan endocrinien, les traitements hormonaux d'affirmation de genre permettent d'induire des changements physiques correspondant à l'identité du genre, mais des études d'efficacité et sécurité de meilleure qualité et au long cours sont nécessaires. La prise en charge de cette population par une équipe spécialisée et multidisciplinaire et l'amélioration de la formation du corps médical sont des mesures indispensables pour le futur.

[News in endocrinology : contemporary treatment of hypothyroidism]. / Endocrinologie : le traitement moderne de l'hypothyroïdie.

Hypothyroidism is the most common hormonal disorder, especially in the female population. Advances in clinical research have allowed more precision in the management of this entity, particularly its subclinical form in the elderly and pregnant women.

L'hypothyroïdie est la pathologie hormonale la plus fréquente, surtout dans la population féminine. Les progrès récents nous ont permis d'être plus précis dans la prise en charge de cette entité, et plus particulièrement de sa forme infraclinique chez le patient âgé et la femme enceinte.

[Endocrinopathies induced by immune checkpoint inhibitors]. / Endocrinopathies induites par les inhibiteurs de points de contrôle immunitaire.

Immune checkpoint Inhibitors are new immunomodulatory treatments that have proven their anti-tumor efficacy in several advanced cancers. Nevertheless, their use has paved the way for multiple immunological adverse effects that affect many systems and organs including endocrine glands such as the pituitary, thyroid, adrenal and pancreas. Hypophysitis is the most common complication of anti-CTLA-4 monoclonal antibodies, while anti-PD-1 and anti-PD-L1 antibodies cause more thyroid complications. Adrenal insufficiency and type 1 diabetes are relatively less common. Endocrinologists and primary care physicians as well as oncologists are likely to deal with these complications and as such, knowledge of these drugs and their side effects is essential for good practice.

Les inhibiteurs de points de contrôle immunitaire sont des nouveaux traitements immunomodulateurs qui ont prouvé leur efficacité antitumorale dans plusieurs cancers avancés. Néanmoins, leur utilisation a ouvert la voie à de multiples effets indésirables immunologiques touchant plusieurs systèmes et organes dont les glandes endocrines comme l'hypophyse, la thyroïde, les surrénales et le pancréas. L'hypophysite constitue la complication la plus fréquente des anticorps monoclonaux anti-CTLA-4, alors que ceux anti-PD-1 et anti-PD-L1 provoquent plus de complications thyroïdiennes. Les insuffisances surrénaliennes et le diabète de type 1 sont relativement moins fréquents. Les endocrinologues et les médecins de premier recours, tout comme les oncologues, sont susceptibles de prendre en charge ces complications et de ce fait, une connaissance spécifique de ces médicaments et de leurs effets indésirables est indispensable à la bonne pratique.

[Endocrinology, what's new in 2016]. / Endocrinologie.

The European Society of Endocrinology has published this year a series of guidelines for hypoparathyroidism, the management of adrenal incidentalomas as well as for the long-term follow-up of patients operated on for a phaeochromocytoma/paraganglioma (PPGL). For hypoparathyroidism, guidelines insist on screening for chronic complications and monitoring treatment with calcium and vitamin D; the use of recombinant PTH may provide new opportunities for the future. Concerning adrenal incidentalomas, the panel of the guidelines primarily recommends non contrast CT for the evaluation of the risk of malignancy. Patients operated on for a PPGL, should be offered an individualized follow-up plan based on assessment of their risk of tumor recurrence.

Des nouvelles recommandations concernant l'hypoparathyroïdie, l'évaluation des incidentalomes surrénaliens ainsi que le suivi à long terme des patients opérés d'un phéochromocytome/paragangliome (PPGL), ont été publiées en 2016 par la Société européenne d'endocrinologie. Pour l'hypoparathyroïdie, l'accent est mis sur l'évaluation des complications chroniques et la titration du traitement par calcium et vitamine D; la supplémentation par PTH-recombinante (rhPTH) est un traitement prometteur. Concernant l'évaluation du risque de malignité des incidentalomes surrénaliens, les études montrent une supériorité de la densité spontanée (DS) de ces tumeurs au CT-scan non injecté, en tant que critère diagnostique. Enfin, un suivi personnalisé est indiqué pour les patients opérés d'un PPGL, après évaluation du risque de récidive à long terme.

[Polycystic ovaries: what's news in 2015?]. / Syndrome des ovaires polykystiques: quoi de neuf?

Polycystic ovary syndrome is a very common endocrine disorder in women of reproductive age, with important clinical implications (fertility issues, hirsutism, metabolic abnormalities). The Endocrine society has published in 2013 a series of diagnostic and treatment recommendations, followed by the European society of endocrinology in 2014. Recently, advances have been made in the measure of androgen biomarker and the evaluation of ovarian morphology with 3D ultrasound techniques. New treatments have emerged for fertility problems associated with the syndrome (ex. letrozole).

[News in endocrinology in 2013]. / Endocrinologie.

Transsphenoidal surgery is the treatment of choice for acromegaly due to pituitary adenoma but it is not always possible to reduce or control tumor growth, inhibit GH hypersecretion and normalize IGF-I. The first-line drug treatment in 2013 remains the somatostatin analogues. In 2012 and 2013 have been published several publications presenting the prognosis of well-differentiated thyroid cancers of intermediate risk. Indeed, the dose of radioactive iodine administered to patients with "favorable" histology in this risk category should be reduced without change in prognosis. Elastograhy could, in combination with conventional ultrasound features, allow a better selection of thyroid nodules that need a cytology, with, however, still limitations in the detection of follicular carcinomas.

Langerhans cell histiocytosis of the suprasellar region: diagnosis based on thyroid cytology.

Langerhans cell histiocytosis (LCH) may present as unifocal disease of the suprasellar region, with symptoms and signs of hypopituitarism, arginine vasopressin deficiency (AVP-D), and weight gain. Transcranial biopsy is necessary to define diagnosis and guide treatment decisions, but it is associated with significant morbidity. We describe a patient with Hashimoto thyroiditis and a single hypothalamic mass in whom LCH diagnosis was made by thyroid fine-needle aspiration cytology (FNAC) performed despite nonspecific findings in thyroid imaging, on the basis of a slightly elevated [18F]-fluorodeoxyglucose (FDG) avidity on PET/CT and volume increase during follow-up.

Differences in surgical outcomes between cervical goiter and retrosternal goiter: an international, multicentric evaluation.

Introduction: Goiter is a common problem in clinical practice, representing a large part of clinical evaluations for thyroid disease. It tends to grow slowly and progressively over several years, eventually occupying the thoracic inlet with its lower portion, defining the situation known as retrosternal goiter. Total thyroidectomy is a standardized procedure that represents the treatment of choice for all retrosternal goiters, but when is performed for such disease, a higher risk of postoperative morbidity is variously reported in the literature. The aims of our study were to compare the perioperative and postoperative outcomes in patients with cervical goiters and retrosternal goiters undergoing total thyroidectomy. Methods: In our retrospective, multicentric evaluation we included 4,467 patients, divided into two groups based on the presence of retrosternal goiter (group A) or the presence of a classical cervical goiter (group B). Results: We found statistically significant differences in terms of transient hypoparathyroidism (19.9% in group A vs. 9.4% in group B, p < 0.001) and permanent hypoparathyroidism (3.3% in group A vs. 1.6% in group B, p = 0.035). We found no differences in terms of transient RNLI between group A and group B, while the occurrence of permanent RLNI was higher in group A compared to group B (1.4% in group A vs. 0.4% in group B, p = 0.037). Moreover, no differences in terms of unilateral RLNI were found, while bilateral RLNI rate was higher in group A compared to group B (1.1% in group A vs. 0.1% in group B, p = 0.015). Discussion: Wound infection rate was higher in group A compared to group B (1.4% in group A vs. 0.2% in group B, p = 0.006). Based on our data, thyroid surgery for retrosternal goiter represents a challenging procedure even for highly experienced surgeons, with an increased rate of some classical thyroid surgery complications. Referral of these patients to a high-volume center is mandatory. Also, intraoperative nerve monitoring (IONM) usage in these patients is advisable.

Hypnosis in High-Intensity Focused Ultrasound for Thyroid Nodule Ablation.

BACKGROUND Current medical technologies enable physicians to treat patients outside operating rooms using minimally invasive techniques. Non-operating room anesthesia (NORA) represents a growing field of medicine, with an increasing number of cases performed over the last decade. As a result, anesthesia providers will need to enhance their understanding of the resources, medical and paramedical staff, and environment outside the operating room. Patients undergoing such procedures under light conscious sedation still experience discomfort such as pain and anxiety, thus requiring the use of pain control medication or sedative drugs. At the same time, the use of hypnosis is spreading in medical practice, particularly with minimally invasive procedures. Many studies have investigated the use of hypnosis in cases of minimally invasive procedures, showing an effective reduction of patients' discomfort and consumption of pain control medication, thus improving patient safety. CASE REPORT We describe the case of a woman in her 70s who underwent a thyroid nodule thermal ablation through high-intensity focused ultrasound (HIFU) performed under hypnosis in a NORA setting. The procedure was well endured; the patient experienced comfort and was satisfied with having avoided general anesthesia. Post-HIFU follow-up showed a 30% decrease of thyroid nodule volume. The patient was completely satisfied with the esthetic result. The operator did not encounter any difficulties with the awoken patient or movements during the procedure. CONCLUSIONS Our case confirms the effective role of hypnosis in relaxation and coping with painful procedures and highlights patient satisfaction without the use of sedative drugs in the context of NORA procedures.

Central node dissection in papillary thyroid carcinoma in the era of near-infrared fluorescence.

The most common site of lymph node metastases in papillary thyroid carcinoma is the central compartment of the neck (level VI). In many patients, nodal metastases in this area are not clinically apparent, neither on preoperative imaging nor during surgery. Prophylactic surgical clearance of the level VI in the absence of clinically suspicious lymph nodes (cN0) is still under debate. It has been suggested to reduce local recurrence and improve disease-specific survival. Moreover, it helps to accurately diagnose the lymph node involvement and provides important staging information useful for tailoring of the radioactive iodine regimen and estimating the risk of recurrence. Yet, many studies have shown no benefit to the long-term outcome. Arguments against the prophylactic central lymph node dissection (CLND) cite minimal oncologic benefit and concomitant higher operative morbidity, with hypoparathyroidism being the most common complication. Recently, near-infrared fluorescence imaging has emerged as a novel tool to identify and preserve parathyroid glands during thyroid surgery. We provide an overview of the current scientific landscape of fluorescence imaging in thyroid surgery, of the controversies around the prophylactic CLND, and of fluorescence imaging applications in CLND. To date, only three studies evaluated fluorescence imaging in patients undergoing thyroidectomy and prophylactic or therapeutic CLND for thyroid cancer. The results suggest that fluorescence imaging has the potential to minimise the risk of hypoparathyroidism associated with CLND, while allowing to exploit all its potential benefits. With further development, fluorescence imaging techniques might shift the paradigm to recommend more frequently prophylactic CLND.

Unnecessary thyroid surgery rate for suspicious nodule in the absence of molecular testing.

Background: Molecular tests for suspicious thyroid nodules decrease rates of unnecessary surgeries but are not widely used due to reimbursement issues. The aim of this study was to assess the rate of unnecessary surgery performed in real-life setting for Bethesda III, IV and V nodules in the absence of molecular testing. Method: This is a single-center retrospective study of consecutive patients undergoing fine needle aspiration cytology (FNAC) with rapid on-site evaluation between January 2017 and December 2021. Unnecessary surgery was defined as surgery performed because of Bethesda III, IV, or V results in the absence of local compressive symptoms with final benign pathology and as second surgery for completion thyroidectomy. Results: In the 862 patients (640 females, mean age: 54.2 years), 1010 nodules (median size: 24.4 mm) underwent 1189 FNAC. Nodules were EU-TIRADS 2, 3, 4, and 5 in 3%, 34%, 42%, and 22% of cases, respectively. FNAC was Bethesda I, II, III, IV, V, and VI in 8%, 48%, 17%, 17%, 3%, and 6%, respectively. Surgery was performed in 36% of Bethesda III nodules (benign on pathology: 81%), in 74% of Bethesda IV nodules (benign on pathology: 76%) and in 97% of Bethesda V nodules (benign on pathology: 21%). Surgery was considered unnecessary in 56%, 68%, and 21% of patients with Bethesda III, IV, and V nodules, respectively. Conclusion: In this real data cohort surgery was unnecessary in more than half of patients with Bethesda III and IV nodules and in 21% of patients with Bethesda V nodules.

The impact of transsphenoidal surgery on pituitary function in patients with non-functioning macroadenomas.

PURPOSE: Transsphenoidal surgery for non-functioning pituitary adenomas (NFPAs) can alter pituitary function. We assessed the rates of improvement and deterioration of pituitary function by axis and searched for predictive factors of these outcomes. METHODS: We reviewed consecutive medical files from patients having had transsphenoidal surgery for NFPA between 2004 and 2018. Pituitary functions and MRI imaging were analyzed prior and after surgery. The occurrence of recovery and new deficit were documented per axis. Prognostic factors of hormonal recovery and new deficits were searched. RESULTS: Among 137 patients analyzed, median tumor size of the NFPA was 24.8 mm and 58.4% of patients presented visual impairment. Before surgery, 91 patients (67%) had at least one abnormal pituitary axis (hypogonadism: 62.4%; hypothyroidism: 41%, adrenal insufficiency: 30.8%, growth hormone deficiency: 29.9%; increased prolactin: 50.8%). Following surgery, the recovery rate of pituitary deficiency of one axis or more was 46% and the rate of new pituitary deficiency was 10%. Rates of LH-FSH, TSH, ACTH and GH deficiency recovery were 35.7%, 30.4%, 15.4%, and 45.5% respectively. Rates of new LH-FSH, TSH, ACTH and GH deficiencies were 8.3%, 1.6%, 9.2% and 5.1% respectively. Altogether, 24.6% of patients had a global pituitary function improvement and only 7% had pituitary function worsening after surgery. Male patients and patients with hyperprolactinemia upon diagnosis were more likely to experience pituitary function recovery. No prognostic factors for the risk of new deficiencies were identified. CONCLUSION: In a real-life cohort of patients with NFPAs, recovery of hypopituitarism after surgery is more frequent than the occurrence of new deficiencies. Hence, hypopituitarism could be considered a relative indication for surgery in patients with NFPAs.

Risk factors for postoperative cervical haematoma in patients undergoing thyroidectomy: a retrospective, multicenter, international analysis (REDHOT study).

Background: Postoperative cervical haematoma represents an infrequent but potentially life-threatening complication of thyroidectomy. Since this complication is uncommon, the assessment of risk factors associated with its development is challenging. The main aim of this study was to identify the risk factors for its occurrence. Methods: Patients undergoing thyroidectomy in seven high-volume thyroid surgery centers in Europe, between January 2020 and December 2022, were retrospectively analysed. Based on the onset of cervical haematoma, two groups were identified: Cervical Haematoma (CH) Group and No Cervical Haematoma (NoCH) Group. Univariate analysis was performed to compare these two groups. Moreover, employing multivariate analysis, all potential independent risk factors for the development of this complication were assessed. Results: Eight thousand eight hundred and thirty-nine patients were enrolled: 8,561 were included in NoCH Group and 278 in CH Group. Surgical revision of haemostasis was performed in 70 (25.18%) patients. The overall incidence of postoperative cervical haematoma was 3.15% (0.79% for cervical haematomas requiring surgical revision of haemostasis, and 2.35% for those managed conservatively). The timing of onset of cervical haematomas requiring surgical revision of haemostasis was within six hours after the end of the operation in 52 (74.28%) patients. Readmission was necessary in 3 (1.08%) cases. At multivariate analysis, male sex (P < 0.001), older age (P < 0.001), higher BMI (P = 0.021), unilateral lateral neck dissection (P < 0.001), drain placement (P = 0.007), and shorter operative times (P < 0.001) were found to be independent risk factors for cervical haematoma. Conclusions: Based on our findings, we believe that patients with the identified risk factors should be closely monitored in the postoperative period, particularly during the first six hours after the operation, and excluded from outpatient surgery.

H2O2 Metabolism in Normal Thyroid Cells and in Thyroid Tumorigenesis: Focus on NADPH Oxidases.

Thyroid hormone synthesis requires adequate hydrogen peroxide (H2O2) production that is utilized as an oxidative agent during the synthesis of thyroxin (T4) and triiodothyronine (T3). Thyroid H2O2 is generated by a member of the family of NADPH oxidase enzymes (NOX-es), termed dual oxidase 2 (DUOX2). NOX/DUOX enzymes produce reactive oxygen species (ROS) as their unique enzymatic activity in a timely and spatially regulated manner and therefore, are important regulators of diverse physiological processes. By contrast, dysfunctional NOX/DUOX-derived ROS production is associated with pathological conditions. Inappropriate DUOX2-generated H2O2 production results in thyroid hypofunction in rodent models. Recent studies also indicate that ROS improperly released by NOX4, another member of the NOX family, are involved in thyroid carcinogenesis. This review focuses on the current knowledge concerning the redox regulation of thyroid hormonogenesis and cancer development with a specific emphasis on the NOX and DUOX enzymes in these processes.

Pulmonary Vein Thrombosis Associated with Metastatic Follicular Thyroid Carcinoma: A Case Report and Review.

Pulmonary vein thrombosis (PVT) mainly occurs following lung transplantation but cases associated with thoracic malignancy have also been described. We describe here the first case of PVT in an asymptomatic patient with metastatic follicular thyroid carcinoma.