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Immune checkpoints inhibitors have fundamentally changed the management of oncologic patients. These treatments consist of monoclonal antibodies directed against CTLA-4 (cytotoxic T-lymphocyte antigen 4), PD-1 (programmed cell death protein-1) and PD-L1 (one of its ligands). By blocking these receptors or ligands, the antibodies reverse the immune tolerance induced by the cancerous cell on the T-lymphocyte and favour lymphocytic reactivation and anti-tumor activity. Immune tolerance to auto-antigens is maintained with the help of these checkpoints. Targeting them can lead to auto-immune side effects. These latter mostly impact the cutaneous and digestive system, but the endocrine glands are not spared. In this article, we provide monitoring and treatment algorithms for these endocrine immune side effects. An early diagnosis followed by the appropriate treatment would reduce their negative impact on the oncologic care.

Les inhibiteurs des checkpoints immunitaires ont considérablement changé la prise en charge des cancers. Ces thérapeutiques sont actuellement représentées par les anticorps monoclonaux anti-CTLA-4 (cytotoxic T-lymphocyte antigen 4), anti-PD-1 (programmed cell death protein-1) et anti-PD-L1 (un de ses ligands). En bloquant ces récepteurs ou ligands, les anticorps contrecarrent le freinage immunitaire instauré par la cellule cancéreuse sur le lymphocyte T et favorisent, alors, la réactivation du lymphocyte et son activité anti-tumorale. Ces checkpoints sont essentiels dans le maintien de la tolérance immune aux auto-antigènes. En les ciblant, des effets secondaires de type auto-immun peuvent apparaître. S'ils privilégient principalement le système cutané et digestif, les glandes endocrines n'en sont néanmoins pas oubliées. Dans cet article, nous suggérons des algorithmes de surveillance et de prise en charge de ces manifestations indésirables endocriniennes. Le diagnostic précoce de celles-ci et leur traitement adéquat permettraient de réduire leur impact négatif sur la prise en charge de la maladie cancéreuse.

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A clinical case of mitochondrial diabetes is reported in a young woman aged 26, also presenting with a neurosensorial deafness. A type MELAS 3243 A>G mutation was found and confirmed the diagnosis which was raised by the maternal history of diabetes and hearing impairment. Clinical description, associated co-morbidities, genetic analysis and differential diagnosis of this monogenic diabetes are presented. Early diagnosis and treatment are useful, and should be associated with a familial genetic diagnostic approach.

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The cardiorenal syndrome is a clinical and pathophysiological concept illustrating the relationship between the two organs, and is mainly based on the control of volemia. Heart failure is an example of this entity: when congestive heart failure becomes refractory, ultrafiltration by various modes of dialysis is needed. Ambulatory peritoneal ultrafiltration is a good alternative for the management of treatment-resistant congestive heart failure. Erythropoietin is the main treatment of anaemia of chronic renal failure for dialysed and predialysed patients, or patients with congestive heart failure and renal insufficiency. Correction of anaemia needs to be controlled at a maximal haemoglobin level of 12 g/dl.

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Sixteen adults patients with insulin-dependent diabetes mellitus and 16 healthy controls, matched for sex and age, were asked to collect their urine during the night and during the day at rest, at weekly intervals on four occasions. Subjects with heart failure, kidney disease, hypertension, abnormal urinalysis (Albustix positive) or poorly controlled diabetes prior to entry in the study, were excluded. A high variability in the albumin excretion rates (AER) was observed in both diabetic and control groups but the variance was significantly greater in diabetics. Moreover the variance in AER was higher in daytime as compared to overnight urine collections in both groups. Overnight urine collections are more precise than daytime urine collections for the determination of AER.

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The precise measurement of glomerular filtration rate (GFR) and renal plasma flow (ERPF) usually requires continuous intravenous administration of adequate substances, with multiple blood and urine analysis, and does not allow measurement of separate renal function. Schlegel et al. and Gates described isotopic methods for the measurement of global and unilateral GFR and ERPF based on the determination by scintillation camera of the fraction of the injected dose ([99mTc]DTPA-[131I]hippuran) present in the kidneys 1-3 min after its administration. These methods require counting of the injected dose and correction for attenuation, but no blood or urine sampling. We have validated these techniques by simultaneous infusion of inulin and PAH in patients with various levels of global renal function (anuric to normal). To better define unilateral renal function we have also studied nine kidneys in patients either nephrectomized or with a nephrostomy enabling unilateral function measurement. A good correlation between inulin or PAH clearances and fractional uptake of [99mTc]DTPA or [131I]hippuran by the kidney was observed. Very good reproducibility of both isotopic techniques was shown. We conclude that determination of the fractional uptake of [99mTc]DTPA and [131I]hippuran between 1 and 3 min allows good and reproducible prediction of global and especially of unilateral kidney function with great rapidity and simplicity, rendering this technique suitable for clinical practice.

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Upper gastrointestinal tract pathology observed at autopsy in 94 patients with end-stage renal disease (GFR less than 10 ml/min) was analysed retrospectively. To better evaluate the effect of haemodialysis on this pathology, the chronic renal failure patients were subdivided into three groups: 19 patients who had died before haemodialysis treatment could be undertaken (group I), 21 patients who had died during the first month (group II), and 54 patients who had died after at least one month of haemodialysis treatment (group III). The results revealed that the number of patients with upper gastrointestinal tract pathology was significantly higher in groups I and II (58% and 57% respectively) as compared to group III (31%) and controls (35%). No difference could be demonstrated between group III and controls. The most prevalent lesions observed were gastritis, followed by gastric and peptic ulcers. The incidence of this pathology appeared to decline as the duration of dialysis therapy increased. Mortality caused by upper gastrointestinal tract pathology remained high during the first two years of treatment in group III, despite a smaller incidence of upper tract lesions. This was explained by a relatively higher proportion of haemorrhage.

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In the light of accumulating evidence implicating the diluting segment as the site of final regulation of sodium excretion by the nephron, we produced in this experiment distal blockade in anti-glomerular basement membrane (GBM) glomerulonephritic (GN) rats by the administration of furosemide and polythiazide. This allowed to dissociate the sodium reabsorption that occurs in the proximal tubule from the one that occurs more distally and permitted an appreciation of the rôle played by the diluting segment in the sodium retention of anti GBM GN. In a previous experiment we showed that GN conscious or anaesthetized rats presented an increase in Na tubular reabsorption and failed to raise their fractional and absolute excretion of sodium as normal one did after rapid volume expansion. In this study distal blockade corrected almost completely the difference in sodium excretion that existed between GN and normal groups before the administration of diuretics, pointing to the important rôle played by the diluting segment in the sodium retention of experimental GN.

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Schlegel and Gates described an isotopic method for the measurement of global and separated glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) based on the determination by scintillation camera of the fraction of the injected dose (99mTc-DTPA-[131I]hippuran) present in the kidneys 1-3 min after its administration. This method requires counting of the injected dose and attenuation correction, but no blood or urine sampling. We validated this technique by the simultaneous infusion of inulin and polycyclic aromatic hydrocarbon (PAH) in patients with various levels of renal function (anuric to normal). To better define individual renal function we studied 9 kidneys in patients either nephrectomized or with a nephrostomy enabling separated function measurement. A good correlation between inulin, PAH clearance, and isotopic GFR-ERPF measurement for both global and separate renal function was observed.

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Considerable discrepancies exist in the literature concerning Na excretion by the rat kidney in experimental antiglomerular basement membrane (GBM) glomerulonephritis (GN). Previous studies in our laboratories demonstrated a disturbance in Na excretion with an impaired absolute (UNa X V) and fractional (FENa) excretion of Na after saline loading. However, most of the other authors in the literature failed to observe similar findings. The present study was undertaken to elucidate some of these controversies: We showed that a difference in Na excretion between anesthetized GN and normal rats might not be detected after a volume expansion if the latter is small or slow (FENa in GN 2 +/- 0.1%, in normals 2 +/- 0.2%; not significant). Only a rapid and important volume expansion is sufficient to unmask such a difference between the two groups (FENa 3 +/- 0.3 and 6 +/- 1%, respectively, p less than 0.001), and detect an impaired Na excretion in GN animals. The same amount of NaCl was nevertheless administered during slow and rapid volume expansion. Similarly, in GN conscious rats only after a saline load or repeated water loads did we observe a significantly smaller UNa X V compared to normals while no difference was present between the two groups after a single water load. In the literature, all the authors, that failed to demonstrate a disturbance in Na excretion in anti-GBM GN, administered slow and small isotonic saline loads to their rats. The hypothesis we formulate to explain these controversies is that the nonobserved disturbance in sodium excretion in most of these studies is probably secondary to insufficient natriuretic stimuli.

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