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.

TRα Mutations in Human.

Resistance to thyroid hormone alpha is an emerging syndrome, with up to now a limited number of published cases. Some features are common to most of the patients, but there is still some work to provide a comprehensive description of the full spectrum of the syndrome. A survey of the strategy to screen for and characterize the mutations in TR α gene is given.

[Somatostatin receptor-based imaging and therapy of digestive endocrine tumors]. / Imageries et traitements basés sur les récepteurs à la somatostatine dans les tumeurs endocrines digestives.

The management of gastroenteropancreatic endocrine tumors is greatly linked to the localization of primary tumor. Morphological imaging methods are thus necessary. However, the expression of somatostatin receptors in endocrine tumors makes their detection possible thanks to radiolabeled somastotatin analogs. [(111)In-DTPA] octreotide is the main radiolabeled analog for somatostatin receptor scintigraphy. Positron emission tomography uses other tracers and currently allows improvement of the diagnosis and the tumoral staging. It also allows to affect the therapeutic management. A further step is about to be taken as far as the therapy of endocrine tumors is concerned with the peptide receptor radionuclide therapy. Those therapies are now being offered in some European and American centers for progressive metastatic tumors. Their place in the therapeutic strategy has to be defined, especially in comparison to targeted therapy. The sudden and delayed adverse events as well as the current legislation on the use of radioactive therapy-aimed products have limited their development in France so far.

Severe episodes of extra cellular dehydration: an atypical adult presentation of cystic fibrosis.

Cystic fibrosis (CF) is usually diagnosed during childhood by respiratory or gastro-intestinal symptoms. Hyponatremic hypochloremic dehydration with metabolic alkalosis is a rare but typical presentation of CF in infants. In contrast, only 3 cases have been described in adults. We report a case of CF in a 33-year-old Caucasian female presenting with a severe sodium and chloride depletion caused by inappropriate sweating. She experienced three episodes of severe dehydration before the diagnosis was suspected. Sweat chloride test was pathological and mild pulmonary involvement was found on CT scan. Delta F508 mutation and a rare mutation (3849+40 A/G) on the intron 19 of CFTR gene were found. Interestingly, our patient has a heterozygote twin sister, carrier of the same mutations of CFTR gene who also developed CF but with a different phenotype. We suspect modifier genes to be implicated in the differences observed between the two phenotypes. We discuss the physiopathology of electrolyte disturbance and review the other similar adults cases.

Distribution of adipose tissue: quantification and relationship with hepatic steatosis and vascular profiles of type 2 diabetic patients with metabolic syndrome.

AIM: As the distribution of fat is increasingly related to cardiovascular events, we examined whether or not abdominal-fat quantification using magnetic resonance imaging (MRI) software is reliable, and whether or not it is related to clinical markers of fat distribution as well as to metabolic and vascular status. METHODS: We recorded the anthropometric measurements of 34 obese type 2 diabetic patients with metabolic syndrome. The patients were enrolled to evaluate their abdominal (visceral and subcutaneous) adipose tissue by single-slice L3-L4 MRI. Manual and automated analyses were compared. The relationships between anthropometric measurements, biological markers and intima-media thickness of the common carotid artery were also assessed. RESULTS: We validated the automated software to quantify abdominal-fat deposition with MRI compared with manual measurements (r2=0.95). The waist-to-hip-circumference ratio (WHR) was the only clinical parameter that correlated with the proportion and quantity of visceral and subcutaneous abdominal-adipose tissue evaluated by MRI (r=0.60). In addition, fat repartition as evaluated by WHR was related to hepatic steatosis parameters (ferritin and ALAT) and to intima-media thickness, whereas simple waist circumference was not a determinant in these obese patients. We also showed that the adiponectin-to-leptin ratio was related to adipose tissue distribution. CONCLUSION: Distribution of abdominal fat, as evaluated by MRI, can be reflected by clinical determination of the WHR. Differences in regional accumulations of abdominal fat may be specifically related to variations in the risks of steatosis and vascular rigidity among obese type 2 diabetic patients.

Endocrine function in a 48,XXYY adult with type 2 diabetes: case report with a review of the literature.

We present the clinical, biological, endocrinal and psychological characteristics of a 48,XXYY adult. The 43-year-old male examined is the first reported case of this XY polysomy concomitant with type 2 diabetes. Endocrine investigations suggested dysfunction of Leydig and Sertoli cells whereas the pituitary function appeared normal. We compare the phenotypic, behavioral and pathological features of the syndrome in our patient with other reports in the literature.

Relevance of Ki-67 and prognostic factors for recurrence/progression of gonadotropic adenomas after first surgery.

OBJECTIVE: Gonadotropin-secreting pituitary adenomas carry a high risk of local recurrence or progression (R/P) of remnant tumor after first surgery. The clinical characteristics and the long-term outcome of these silent adenomas, which show no signs of endocrine hyperfunction, differ from those of other types of pituitary adenomas. However, to date, no study has focused specifically on gonadotropic adenomas. MATERIALS AND METHODS: To identify prognostic factors of R/P of remnants, we studied the postoperative outcome of 32 gonadotropic pituitary adenomas, defined on immunohistochemical staining, according to their clinical and radiological characteristics as well as the Ki-67 labeling index (LI). RESULTS: The Ki-67 LI failed to provide independent information for the identification of patients at risk of progression of remnants or recurrence. Multivariate survival analysis (Cox regression) showed that neither invasiveness nor remnant tumors nor hyposomatotropism influenced tumor recurrence. The strongest predicting factors of R/P were the antero-posterior (AP) diameter in the sagittal plane (P = 0.014), and the age of the patient at surgery (P = 0.047), with younger patients being at greater risk. Hazard ratios were 2.11 for each 5 mm increase in AP diameter and 0.57 for every 10 years of age. CONCLUSION: The two simple clinical criteria revealed by our study, the AP diameter of the tumor and the age of the patient, should be helpful in planning clinical management and radiological monitoring after first surgery of gonadotropic adenomas, while awaiting the identification of other pathological parameters.

[Use of cabergoline in persisting Cushing's disease]. / Utilisation de la cabergoline dans la maladie de Cushing non contrôlée.

Cabergoline is a dopaminergic agonist with demonstrated efficiency of for the treatment of prolactin-secreting pituitary tumors. It has also been reported effective for patients with hypercortisolism uncontrolled by conventional therapies. We describe the use of cabergoline in three patients with Cushing's disease, one of them presenting a silent ACTH-secreting pituitary tumor. Those patients underwent surgery and only one has been treated with radiation therapy. However persisting hypercortisolism motivated the use of cabergoline. We describe a decrease or a normalization in hypercortisolism; for one of the subjects, tumor growth seemed to be stopped. While cabergoline can induce a suppression of cortisol secretion or a corticotroph tumor shrinkage, the sites of action remain unclear.

[Peculiarities of the emergency care in pregnant women]. / Particularités de la prise en charge des urgences chez la femme enceinte.

Awareness of the physiological changes associated with pregnancy is essential for the management of patients during pregnancy. Cardiovascular status is characterised by hypervolemia and cardiac hyper-output with low resistance. Increased oxygen consumption and respiratory work result in an increased risk of hypoxia. Fetal well-being must also be taken into account. During cardiorespiratory arrest, aortocaval compression by the pregnant uterus may impair the efficacy of CPR and uterine displacement is a routine measure starting from 20 weeks after the LMP. The same factors are involved in hemorrhagic shock, justifying uterine displacement and the ensuring of optimal oxygen transport and utilisation.