SFE-AFCE-SFMN 2022 consensus on the management of thyroid nodules: Synthesis and algorithms.

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 and 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), the French Association of Endocrine Surgery (AFCE) and the French Society of Nuclear Medicine (SFMN); the various working groups included experts from other specialties (pathologists, radiologists, pediatricians, biologists, etc.). This specific text is a summary chapter taking up the recommendations from specific sections and presenting algorithms for the exploration and management of thyroid nodules.

[Endocrine side effects of radiation therapy: Diagnosis, prevention, and treatment]. / Effets secondaires endocriniens de la radiothérapie : diagnostic, prévention et traitements.

Endocrine complications after radiotherapy are usually delayed and require prolonged follow-up by the radiation oncologist. Endocrine glands are dispersed throughout the body and can be included in the radiation field of several tumors. As the symptomatology can sometimes be insidious and non-specific, their screening is based on a directed clinical examination but also on systematic hormonal assays. The thyroid gland is particularly radiosensitive, and hypothyroidism is generally observed for doses of more than 30Gy. After cervical irradiation, it is recommended to perform a TSH assay every 6 to 12months. The risk of secondary thyroid cancer only concerns children and exists even at low doses, systematic screening is required. The risk of pituitary insufficiency is dose-dependent, with different sensitivity for each axis. In children, the main concern is the early detection of somatotropic insufficiency in order to prevent the risk of short stature. Reproductive function can be impaired after receiving 4-6Gy requiring fertility preservation. Endocrine side effects can be treated to improve quality of life; therefore, we propose several approaches to be followed in order to promote screening and treatment.

[Graves' orbitopathy: diagnosis, epidemiology and treatments]. / L'orbitopathie basedowienne: diagnostic, épidémiologie et principes de traitement.

Graves' orbitopathy is the most common extra-thyroid complication of Graves' disease and can be a potentially severe affection, therefore requiring multidisciplinary treatment support according to clinical activity and severity assessments. This review proposes to determine physiopathological mechanisms, epidemiology and therapeutic management of Graves' orbitopathy.

[Diagnostic approach and therapeutic management of hyperthyroidism]. / Démarche diagnostique et prise en charge thérapeutique de l'hyperthyroïdie.

Hyperthyroidism is a frequent clinical situation that can be expressed by various signs and it is generally easy to diagnose. This review proposes to explain the diagnostic approach that affects therapeutic management by separating diseases with homogeneous and nodular thyroid.

Digestive symptoms in daily life of chronic adrenal insufficiency patients are similar to irritable bowel syndrome symptoms.

Gastrointestinal symptoms are frequent in acute adrenal insufficiency. Although digestive symptoms can significantly reduce quality of life, they are rarely described in patients with treated chronic adrenal insufficiency (CAI). We aimed to characterize digestive symptoms in CAI patients. We used the section pertaining functional bowel disorders of the Rome IV questionnaire. A questionnaire was published on the website of the non-profit patient association "Adrenals" (NPPA of CAI patients) for five months. Information on demographics, characteristics of adrenal insufficiency, digestive symptoms and quality of life was collected. The relatives of CAI patients served as a control group. We analyzed responses of 33 control subjects and 119 patients (68 primary adrenal insufficiency (PAI), 30 secondary adrenal insufficiency (SAI) and 21 congenital adrenal hyperplasia (CAH)). Abdominal pain at least once a week over the past 3 months was reported by 40%, 47% and 33% of patients with PAI, SAI and CAH respectively versus 15% for the controls (p = 0.01). Symptoms were consistent with the Rome IV criteria for irritable bowel syndrome in 27%, 33% and 33% of patients respectively versus 6% for the controls (p < 0.0001). Quality of life was described as poor or very poor in 35%, 57% and 24% of patients respectively versus 5% for the controls (p < 0.0001). In conclusion, digestive symptoms are frequent and incapacitating in CAI patients and similar to symptoms of irritable bowel syndrome in 30% of CAI patients. Assessment and management of digestive symptoms should be considered a priority for physicians treating patients with CAI.

Thyroid surgery in obese patients: A review of the literature.

The incidence of obesity in the general population has tripled in the past four decades. The number of bariatric surgeries performed annually has quadrupled in the past ten years due to this obesity epidemic. Concomitantly, the number of patients who are obese or who have undergone bariatric surgery and have become candidates for thyroid surgery has also increased considerably. Among patients undergoing thyroidectomy in the French population, the proportion of obese patients currently represents 10 to 20%. In addition, the frequency of benign and malignant thyroid pathologies seems to be increased by obesity, with a Hazard Ratio of around 1.8 for thyroid cancers in obese women. While obesity does not seem to influence the specific post-operative morbidity of thyroidectomy, a history of malabsorptive bariatric surgery should encourage the greatest caution in patients who need to undergo thyroid surgery since it is associated with a significant risk of severe hypocalcemia (>60% in some studies) requiring intravenous calcium supplementation in about 20% of cases. In the latter situation, peri-operative vitamin D-calcium supplementation is essential. In addition, the replacement dose of Levothyroxine (T4) intended for replacement must also be adapted in obese patients, calculated not from the actual weight but from the ideal weight. The objective of this review is to discuss the influence of obesity on the evolution of nodular and neoplastic thyroid pathologies, on the morbidity of thyroid surgery as well as on post-operative drug treatments. The impact of bariatric surgery on these different aspects is also discussed.

Non-adrenal tumors of the adrenal area; what are the pitfalls?

Discovery of an adrenal mass is nowadays a frequent situation. While adrenal tumors can cause a variety of symptoms, more often than not they are diagnosed incidentally on imaging exams such as CT-scan or MRI performed for another purpose. However, any retroperitoneal supra-renal mass can have an extra-adrenal origin. Indeed, operated non-adrenal masses initially but wrongly diagnosed as an adrenal disease represent about 3.5% of adrenalectomies. These differential diagnoses principally include retroperitoneal tumors that are malignant in two thirds of cases (lymphomas, sarcomas, neurogenic or germinal tumors), and more rarely vascular anomalies or congenital malformations, which are most frequently left-sided due to the wide variety of anatomical structures surrounding the left adrenal gland. Several lesions can originate from the adrenal gland or be located near the gland (paraganglioma, ganglioneuroma). Even though unilateral adrenalectomy is associated with low morbidity, ignorance of these differential diagnoses can cause ill-adapted management; overly conservative surgery in case of sarcoma is one example. Some of these lesions have characteristic clinical or imaging features (cystic lymphangioma, angiomyolipoma…). In other cases, assessment of hormonal secretion is required and additional exams (MRI, percutaneous biopsy, PET-scan with 18-Fluorodeoxyglucose) can correct an erroneous diagnosis. The above diagnostic approach allows appropriate management (with or without surgery). The purpose of this review was to highlight the main differential diagnoses of adrenal masses, to describe their characteristics, and to discuss their therapeutic management.

French Endocrine Society Guidance on endocrine side effects of immunotherapy.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPIs). However, the use of ICPI has a risk of side effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a consensus document on ICPI-related endocrine toxicity. In this paper, we will introduce data on the general pathophysiology of endocrine toxicity, and we will then outline expert opinion focusing primarily on methods for screening, management and monitoring for endocrine side effects in patients treated by ICPI. We will then look in turn at endocrinopathies that are induced by ICPI including dysthyroidism, hypophysitis, primary adrenal insufficiency and fulminant diabetes. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. These expert opinions will also discuss the methodology for categorizing these side effects in oncology using 'common terminology criteria for adverse events' (CTCAE) and the difficulties in applying this to endocrine side effects in the case of these anti-cancer therapies. This is shown in particular by certain recommendations that are used for other side effects (high-dose corticosteroids, contraindicated in ICPI for example) and that cannot be considered as appropriate in the management of endocrine toxicity, as it usually does not require ICPI withdrawal or high-dose glucocorticoid intake.

[Kidney full of stones, and an adrenal gland not quite normal]. / Des reins pleins de cailloux, et une surrénale pas tout à fait normale.

A 31-year-old patient was followed for cystinuria, justifying CT scans. In 2006, a tissue mass of 3cm of the right adrenal gland, homogeneous, measured at 3.5cm in 2007 was noted. Blood pressure was 90/61mmHg, without orthostatic hypotension. During the clinical interview, no discomfort, sweat attack, headache, or palpitation was reported by the patient. Hormonal assays did not favor a primary hyperaldosteronism, or a hypercortisolism. Adrenal androgens were normal. 24h normetanephrines urinary excretion and metanephrines to creatinine ratio were elevated. One year later, the patient remained asymptomatic and normotensive. Plasma levels of normetanephrine and metanephrine were increased and highly pathological. The tumor was 5cm long and fixed individually on MIBG scintigraphy and PET scan. Right adrenalectomy was performed. A pheochromocytoma was confirmed histologically. The peculiarity here was the absence of symptoms, especially arterial hypertension. This currently affects up to 47% of cases, particularly in the context of incidentaloma investigations and family screening. Indeed, 35 to 40% of pheochromocytomas are associated with a germline mutation, justifying a genetic analysis in this patient. Genetic analysis did not show any mutation associated with pheochromocytoma. At a 6-year interval pheochromocytoma did not reappeared while BP increased reaching hypertension threshold. The only documented recurrence was lithiasis.

Factors predictive of lymph node metastasis in the follicular variant of papillary thyroid carcinoma.

BACKGROUND: The treatment of papillary thyroid carcinomas larger than 1 cm usually consists of total thyroidectomy and central lymph node dissection (LND). In patients with the follicular variant of papillary thyroid carcinoma (FVPTC), preoperative cytology and intraoperative frozen-section analysis cannot always establish the diagnosis. The aim of this study was to evaluate predictive factors for lymph node metastasis in patients with FVPTC and to identify patients who might benefit from LND. METHODS: The study included patients with FVPTC treated by total thyroidectomy and LND between 2000 and 2010 in four departments. When fewer than six non-involved lymph nodes were removed, the patient was excluded from the analysis. RESULTS: Some 199 patients were included. The median tumour size was 17 (range 1-85) mm, and tumours were classified as T1a in 28 patients, T1b in 40, T2 in 53, and T3 in 78. Eighty-one patients (40·7 per cent) had lymph node metastasis (51 classified as N1a and 30 as N1b). Four risk factors were predictive of lymph node metastasis in the multivariable analysis: multifocality (odds ratio (OR) 2·36, 95 per cent confidence interval 1·15 to 4·86), angiolymphatic invasion (OR 3·67, 1·01 to 13·36), absence of tumour capsule (OR 3·00, 1·47 to 6·14) and tumour involvement of perithyroid tissue (OR 3·89, 1·85 to 8·18). The rate of lymph node metastasis varied between 14 and 94 per cent depending on the presence of risk factors. CONCLUSION: The rate of lymph node metastasis in patients with FVPTC varies widely according to the presence or absence of predictive risk factors.

(18)F-FDG uptake at initial staging of the adrenocortical cancers: a diagnostic tool but not of prognostic value.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. (18)F-FDG PET ((18)F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, (18)F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative (18)F-FDG PET based on SUVs assessments has a prognostic value in ACC patients. METHODS: A retrospective analysis was performed in patients who underwent (18)F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; (18)F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All (18)F-FDG PET/CT procedures were reinterpreted in a blind fashion. RESULTS: Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)(max) = 11 (range: 3-56) and a tumor/liver SUV(max) ratio = 4.2 (range: 1.3-15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. (18)F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis. CONCLUSIONS: At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.

Pheochromocytoma revealed by acute heart failure. When should we operate? Presented at the ESES Congress, Gothenburg May 25-26, 2012.

PURPOSE: The aim of this study was to assess the safety and efficacy of adrenalectomy on patients with pheochromocytoma diagnosed at the time of an acute heart failure (AHF). METHODS: We reported cases of patients who presented an AHF secondary to a pheochromocytoma during a period of 10 years. The diagnosis of AHF was defined by a left ventricular ejection fraction of less than 30 % or the use of circulatory assistance. They had adrenalectomy as emergency surgery or later. Morbidity and mortality of surgery were studied. RESULTS: Thirteen patients required an adrenalectomy for AHF secondary to pheochromocytoma. Four patients (31 %) had an adrenalectomy in emergency. Nine patients (69 %) had a delayed surgery with a median delay of 25 days (7-180). Eight patients had circulatory assistance (61 %). Five of them had a circulatory assistance and a delayed surgery (38 %), two of them had a circulatory assistance followed by emergency surgery (at 1.5 and 3 days) and one had emergency surgery immediately followed by circulatory assistance. Emergency surgery was performed by laparotomy in all cases and delayed surgery by laparoscopy for seven patients (54 %). Perioperative complications consisted in: one circulatory arrest, two bleedings requiring transfusion, one intestinal ischaemia, one haemoperitoneum with re-operation (day 8). One patient died on day 5. Post-operative course of patients with delayed surgery was uneventful. CONCLUSIONS: AHF revealing a pheochromocytoma is a rare and serious event. Patients with emergency surgery have more complications than those with delayed surgery.

Fulminant type 1 diabetes in Caucasians: A report of three cases.

CONTEXT: Fulminant type 1 diabetes is a new clinical entity in which the process of beta-cell destruction, and the subsequent progression of hyperglycaemia and ketoacidosis, are extremely rapid. Until now, this subtype of type 1 diabetes has only been reported in the Asian population, especially Japanese and Koreans. CASES: We report here on three cases of fulminant type 1 diabetes in Caucasian French women. Both the clinical and biological characteristics of these patients are similar to those reported in Japanese studies. Notably, all patients experienced severe ketoacidosis (pH<7.1) that occurred abruptly after the onset of hyperglycaemic symptoms (<6 days), with near-normal HbA(1c) values at diagnosis (5.6, 6.4 and 6.8%). Patients were treated in the intensive care unit with basal-bolus insulin therapy with no remission of their diabetes; pancreatic islet-related autoantibodies were all negative. Fasting C-peptide levels were undetectable, suggesting complete destruction of pancreatic beta-cells. HLA phenotyping of these Caucasian patients did not find the specific HLA haplotype (DRB1*0405-DQB1*0401) previously found to be linked to fulminant type 1 diabetes in Japanese patients. CONCLUSION: These are the first cases of fulminant type 1 diabetes reported in Caucasians. These cases reveal new perspectives as regards the worldwide distribution of this intriguing clinical entity.