[Gastric mucosal calcinosis]. / Calcinose de la muqueuse gastrique.

The gastric mucosal calcinosis is a benign condition corresponding to calcium deposits in the gastric mucosa. A 39-year-old women, with an history of transplantation, transplant rejection and hemodialysis, treated with corticosteroids and calcium/phosphoremic supplements, had chronic diarrhea. Gastroduodenal fibroscopy found an atypical atrophic gastritis appearance with small focal whitish deposits in the gastric mucosa. Histological examination revealed brown and gray-bluish crystalline deposits in superficial chorion, stained by Von Kossa, leading to a diagnosis of gastric mucosal calcinosis. This lesion can be categorized as systemic, dystrophic, iatrogenic and idiopathic. In our observation, gastric mucosal calcinosis was probably mixed, linked to renal disorders, and mainly to exogenous phosphocalcic drug intakes. The gastric mucosal calcinosis is commonly found  in kidney transplant patients reaching a frequency of 15 to 29%.

[Pathological and molecular features of malignancies underlined by BAF complexes inactivation]. / Aspects morphologiques et moléculaires des tumeurs malignes associées à une dérégulation des complexes BAF.

BAF complexes are chromatin remodelling complexes made up of 15 subunits which overview transcription regulation. A subset of their subunits are notoriously linked to cancer, with the examples of SMARCB1, SMARCA4, ARID1A/1B and PBRM1. The complexes act as tumor suppressor genes, commonly mutated in a wide array of malignancies with an overrepresentation of sarcomas and tumors of the central nervous system. The recurrent inactivation of their genes points towards their driving role in the tumorigenesis of SMARCB1 in malignant rhabdoid tumors and SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type. These tumors are morphologically similar composed of solid sheets of cells displaying vesicular nuclei dotted with clear chromatin and conspicuous nucleoli. Genomically, they share simple diploid profiles with no other alterations than in the culprit gene. Other mesenchymal tumors, distinct from malignant rhabdoid tumors are associated with BAF alterations, namely epithelioid sarcomas, SMARCA4-deficient thoracic sarcomas. BAF subunits are mostly inactivated through mutations or deletions but also occur through translocations in medullary carcinoma of the kidney and synovial sarcomas. Apart from tumors displaying recurrent alterations of the complexes, some variants or tumor variants display BAF alterations, including epithelioid malignant peripheral nerve sheet tumors and poorly differentiated chordomas. Lastly, some malignancies display low frequency of BAF alterations, in keeping with their passenger role in tumorigenesis with the example of dedifferentiated carcinomas, especially in colon, lung and uterus. BAF complexes alterations correlate with morphological features recognizable by microscopy, paving the way for their routine diagnosis and potential therapeutic prospects.

[A e-Hypercalcemia]. / À propos d'une e-Hypercalcémie.

INTRODUCTION: Hypercalcemia is a common biological abnormality. The etiologies are mainly represented by hyperparathyroidism and neoplastic causes. The other causes, including poisoning, are rare, but should not be neglected. OBSERVATION: An 82-year-old female patient presented to the emergency room for repeated falls at home, confusion, drowsiness and digestive symptoms. The initial assessment showed hypercalcemia above 3mmol/L. The etiological exploration revealed a very high concentration of 25OH-vitamin D. After repeated interrogations, it appeared that the cause of this intoxication was the intake of a food supplement purchased on the internet, following a prescription from her dentist. CONCLUSION: Intoxication due to a food supplement containing vitamin D is possible and potentially serious. Raising the awareness of patients and healthcare professionals is necessary in order to prevent this type of poisoning and/or to diagnose it as soon as possible.

[Electrolyte disorders in oncological patients]. / Principaux troubles hydro-électrolytiques chez le patient de cancérologie.

Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by the cancer, its therapy or paraneoplastic syndromes. ED are associated with poor outcomes, increased morbidity and mortality in this population. Hyponatremia is the most common disorder, often multifactorial, iatrogenic or secondary to the syndrome of inappropriate antidiuretic hormone secretion, usually due to small cell lung cancer. More rarely, hyponatremia may reveal adrenal insufficiency. Hypokalemia is generally multifactorial and associated with other ED. Cisplatin and ifosfamide induce proximal tubulopathies with hypokalemia and/or hypophosphatemia. Hypomagnesemia is often iatrogenic, related to cisplatin or cetuximab, but can be prevented by supplementation. Hypercalcemia can impair life quality and be life-threatening in the most severe cases. Hypocalcemia is less common and often of iatrogenic origin. Finally, the tumor lysis syndrome is a diagnostic and therapeutic emergency that affects the prognosis of patients. Its incidence tends to increase in solid oncology, related to the improvement of therapies. Prevention and early diagnosis of ED are essential to optimize the overall management of patients with underlying cancer and cancer therapy. The aim of this review is to synthesize most frequent ED and their management.

Iatrogenic endocrine complications of lithium therapy.

Lithium is a cation, similar to sodium and potassium, affecting ion transport. It is used in the medical field as a treatment of bipolar disorders. The main endocrine complications of lithium treatment affect thyroid and parathyroid glands, in association with renal complications. Thyroid adverse effects, which are more frequent in women, comprise hypothyroidism, goiter, or sometimes hyperthyroidism, through interference with the iodine symporter. The increase in thyroid volume is early. Prevalence of goiter is 4 times higher than in the general population and hypothyroidism (8-20%) more frequent in case of pre-existing thyroid autoimmunity. Hyperthyroidism likely to worsen mood is reported in 5% of cases but the causal link to lithium is unproven. An increase in serum calcium and PTH occurs in 30% of cases, as lithium stimulates parathyroid cell proliferation by activating the Wnt pathway. The risk of hyperparathyroidism, by adenoma and especially by hyperplasia, is 5 times higher than in the general population, with the particularity of frequent low urine calcium by action on the calcium-sensing receptor (CaSR). Renal complications include risk of acute or chronic renal failure and nephrogenic diabetes insipidus, which is a factor for hypernatremia and hypercalcemia through dehydration. Nephrogenic diabetes insipidus is not always reversible after lithium therapy discontinuation. Metabolically, weight gain can be observed, but rather less than with other psychotropic drugs, and lithium does not in itself induce diabetes. At pituitary level, corticotropic activation is frequent, but implicating the disease rather than lithium. Lithium treatment induces little or no hyperprolactinemia. Regular monitoring of serum calcium, the ionogram, creatinine and TSH is recommended in lithium treatment.

Poor performance of albumin or protein-adjusted plasma calcium to diagnose dyscalcemia in hospitalized patients: A confirmatory study in a general internal medicine department.

INTRODUCTION: Hypo- and hypercalcemia are common and some causes require urgent diagnosis and treatment. Measurement of ionized calcium is the reference test to diagnose calcium disorders but total calcium adjusted for protein or albumin concentration is more often used. METHODS: Patients hospitalised in a general internal medicine department from September 2013 to December 2015 who had a total plasma calcium concentration and a serum albumin or protein concentration measured within 24h of a ionized calcium blood measurement were included. Total calcium was adjusted for protein or albumin concentration using widely used formulas and compared to ionized calcium as the gold standard. RESULTS: Among 210 included patients, 46 (22%) had hypocalcemia, 124 (59%) normocalcemia and 40 (19%) hypercalcemia according to ionized calcium concentration. Total calcium had 50% sensitivity and 95% specificity to diagnose hypocalcemia and a 93% sensitivity and 89% specificity to diagnose hypercalcemia. Adjusting total calcium for protein or albumin concentrations did not increase and sometimes decreased diagnostic accuracy. CONCLUSION: Total calcium, with or without albumin/protein adjustment, is poorly sensitive to screen for hypocalcemia. Unadjusted total calcium is as sensitive as protein- or albumin-adjusted total calcium to screen for hypercalcemia. These data argue against the use of albumin- or protein-adjusted calcium. Ionized calcium measurement should be performed to confirm dyscalcemia in patients with abnormal total calcium concentration and to rule out hypocalcemia in patients with total calcium concentration in the lower range of normal values.

[Renal involvement in sarcoidosis: Prognostic and predictive factors]. / Atteinte rénale au cours de la sarcoïdose : facteurs pronostiques et prédictifs.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease that primarily affects the respiratory system and lymphatic vessels. Renal involvement is rare, poorly studied and found in less than 10% of cases. The objective of our study was to identify factors of poor renal prognosis and predictive factors of renal involvement during sarcoidosis. METHODS: It's a retrospective study including patients hospitalized in our department for sarcoidosis with renal involvement over a period of 40 years. To study renal survival, we identified two groups of patients with renal manifestations of sarcoidosis by following their evolution: group A (n=26) represents those with renal remission or deterioration of renal function but without progression to end-stage renal disease and group B (n=8) those with progression to end-stage renal disease. To detect the predictive factors of end-stage renal disease in patients with sarcoidosis, we compared the clinical and paraclinical characteristics of our patients (group 1) to those of 44 patients with sarcoidosis without renal impairment followed in our department during the same period (group 2). RESULTS: Renal involvement was observed in 34 patients hospitalized for sarcoidosis (43.6%). There were 28 women and 6 men with a sex ratio of 0,21. The mean age at diagnosis of sarcoidosis was 47.1 years. The median time from sarcoidosis diagnosis to renal disease was 2 months (range 1-72). Tubulointerstitial nephropathy was the most frequent renal manifestation observed in 24 patients (70.6%). Hypercalcemia and hypercalciuria were found in 52.9% and 46.4% respectively. Renal failure was noted in 25 patients (73.5%). Corticosteroid therapy was initiated in 33 patients (97%) associated with immunosuppressive therapy in 3 cases. Predictive factors of end-stage renal disease were advanced age at diagnosis of nephropathy (P=0.007), comorbidities (P=0.002), multi-organ involvement (P=0.041), initial renal failure (P=0.013), interstitial fibrosis (P=0.006) and renal granulomas (P=0.007). Predictive factors of renal impairment during sarcoidosis were multi-organ involvement, inflammatory syndrome and hypercalcemia. CONCLUSION: Renal envolvement, although rare during sarcoidosis, can influence the prognosis hence the great interest of its early detection to prevent progression to end-stage renal failure.

[Diagnostic trap: Lithium neurotoxicity with normal lithemia]. / Piège diagnostique : neurotoxicité au lithium avec lithémie normale.

We describe here the case of a 54-year-old bipolar woman, followed in psychiatry and treated with lithium and a selective serotonin reuptake inhibitor (escitalopram) and lamotrigine, presenting a lithium poisoning with an altered state of consciousness caused by a supposed mismanagement of her treatment. Lithium poisoning was suggested based on neurological clinical features, but the blood test brought out a lithium concentration within the therapeutic values at 1,2 mmol/L (N: 0,6-1,2 mmol/L). The classic biological complications related to lithium poisoning (hypercalcemia, diabetes insipidus) confirmed the diagnosis. The patient has been transferred to our nephrology department where she got two hemodialysis sessions conducting to clinical and biological improvement, confirming the diagnosis of lithium poisoning despite the normal blood levels. Later, she was transferred to the psychiatry department for follow-up and for treatment adjustment.

[Hypercalcemia - Diagnosis and Management]. / Hyperkalzämie ­ Diagnose, Abklärung und Therapie.

Hypercalcemia - Diagnosis and Management Abstract. The diagnostic workup of hypercalcemia requires a thorough patient history, a focused clinical examination as well as a step-by-step laboratory diagnostic approach. In order to detect the exact aetiology of hypercalcemia an accurate measurement of serum calcium in correlation with the parathyroid hormone level is therefore essential. Primary hyperparathyroidism and malignancy-related hypercalcemia are responsible for about 90% of all hypercalcemia cases. Therefore, these two pathologies should always be considered in the diagnostic approach. The therapeutic procedure is based on the aetiology and severity of the hypercalcemia.

[Unexpected Postoperative Diagnosis of Parathyroid Carcinoma]. / Unerwartete postoperative Diagnose eines Nebenschilddrüsenkarzinoms.

Unexpected Postoperative Diagnosis of Parathyroid Carcinoma Abstract. Parathyroid carcinoma is a rare endocrine malignancy. It typically presents itself with similar clinical features as seen in patients with primary hyperparathyroidism caused by a parathyroid adenoma. Due to overlapping clinical manifestations, imaging findings and pathological characteristics, the differentiation between benign and malignant parathyroid disease poses a diagnostic challenge, especially prior to surgery. We report the case of a 67-year-old male who presented with symptomatic hypercalcemia and primary hyperparathyroidism. During resection of the enlarged parathyroid gland, suspicious macroscopic features were noticed and the histopathology finding confirmed the malignancy. Parathyroid carcinoma is rarely diagnosed preoperatively, which is mainly due to the lack of distinctive symptoms or morphological features suggesting a malignant disease. As parathyroid carcinoma often has a genetic background, knowledge of mutation status and family history is of high relevance. Surgery with complete resection of the parathyroid carcinoma is the mainstay for a successful treatment and a good prognosis.

[Chronic metabolic and renal disorders related to lithium salts treatment]. / Complications métaboliques et rénales chroniques du traitement par sels de lithium.

Lithium salts are the main treatment of bipolar disorder, which is characterized by potentially life-threatening maniac and/or depressive episodes. They have proven efficient in the prevention and treatment of acute episodes as well as in the prevention of suicidal risk. However, this efficacy is counterbalanced by a narrow therapeutic range that can lead to potentially harmful overdose, and by adverse long-term events. Nevertheless, they remain first-line treatment, notwithstanding therapeutic alternatives. In this review, we will describe toxic effects of long-term treatment at therapeutic levels of lithium salts. Regarding renal effects, early-impaired urine concentrating ability might lead to polyuria and polydipsia, and even to hypernatremia if free access to water is compromised. Long-term lithium treatment might also lead to chronic kidney disease, characterized by tubulo-interstitial multicystic nephropathy. End-stage renal disease requiring renal replacement therapy is a rare complication. Major extra-renal toxic effects are hypercalcemia and hypothyroidism. Treatment cessation due to these adverse events should be a multidisciplinary and case-by-case decision based on the benefit/risk ratio. Since these toxic effects are mild and display slow progression, treatment cessation is uncommon. However, regular medical and biological check-up is needed in order to prevent these disorders, and patients might be referred to nephrologists and/or endocrinologists once the disorders are established.

[Echo-guided splenic biopsy: An effective diagnostic tool in sarcoidosis?] / La biopsie splénique échoguidée : un outil diagnostique efficient au cours de la sarcoidose ?

BACKGROUND: Histological diagnosis of systemic granulomatosis may be difficult. The question of the best histological target remains unanswered. CASE: We report here the observation of a patient admitted in intensive care unit for severe hypercalcemia in the context of polylymphadenopathy and constitutional symptoms. Assessment of this hypercalcemia was suggestive of systemic granulomatosis. The CT (computed tomodensitometry) revealed lymphadenopathies of the mediastinum and the hepatic hilus, hepatomegaly and heterogeneous splenomegaly. At this stage, our main hypotheses were: lymphoid hematopathy, sarcoidosis, tuberculosis. An echo-guided biopsy of the spleen allowed the histological diagnosis of systemic granulomatosis suggestive of sarcoidosis, without significant complication in the course. CONCLUSION: This observation illustrates the efficiency and safety of spleen biopsy for the histological diagnosis of systemic granulomatosis.

[Hyperthyroidism-induced calciphylaxis: A case report]. / Calciphylaxie dans un contexte de maladie de Basedow : à propos d'un cas.

BACKGROUND: Calciphylaxis or calcific uremic arteriolopathy (CUA) is a cutaneous disease with ulcerations secondary to calcification of cutaneous and subcutaneous small arteries and arterioles. It is a rare but severe disease with significant morbidity and mortality affecting 1 to 4% of dialysis patients. The circumstances of occurrence are multiple. CASE: We report the case of a severe bilateral lower limb calciphylaxis in a 69-year-old, obese, hemodialysis patient with a recent diagnosis of Graves' disease complicated with hypercalcemia and cardiac arrhythmia requiring the use of vitamin K antagonist. Complex and multidisciplinary therapeutic management (daily hemodialysis, sodium thiosulfate therapy, treatment of hypercalcemia by denosumab, hyperbaric oxygen therapy, meshed skin autograft) allowed complete healing of the lesions. CONCLUSION: This is the first description of AUC secondary to hyperthyroidism in a dialysis patient. Multidisciplinary care is essential to achieve clinical improvement in those critical situations.

[Life-threatening hypercalcemia and acute kidney injury induced by etanercept]. / Hypercalcémie sévère et insuffisance rénale aiguë induites par étanercept.

Drug-induced sarcoidosis-like disease is a rare, but not exceptional, side effect of anti-tumor necrosis factor (anti-TNF) agents. The organs most commonly involved are lungs, skin and lymph nodes. Kidney involvement is exceptional. Histology usually reveals non-caseating granulomas. Some of the biological features usually described in sarcoidosis are very infrequent in drug-induced granulomatosis. We report a case of sarcoid-like granulomatosis manifesting as life-threatening hypercalcemia and acute kidney injury in a woman treated with etanercept for a rheumatoid arthritis. Seven days after admission, she developed hypoxemic interstitial pneumonia with negative mycobacterial and fungal analysis. This picture suggested sarcoid-like disease induced by tumor necrosis factor blockers and prompted etanercept cessation. Kidney biopsy performed 30 days after admission revealed significant acute interstitial nephritis and intratubular calcium crystals. Staining for acid-fast bacilli and fungi was negative. Clinical picture improved gradually after etanercept withdrawal and cortisone treatment. Three weeks after admission, serum creatinine and calcium levels were normal. Clinical presentation of sarcoidosis-like disease induced by anti-tumor necrosis factor agents may be extremely variable. Our observation shows that severe, life-threatening hypercalcemia may occur. Renal involvement is very unusual. This case highlights this diagnostic difficulty and the importance of a close clinical monitoring in patients treated with these drugs. Cessation of the anti-tumor necrosis factor agent leads to resolution of this condition in most cases.

[Severe hypercalcemia of unusual cause, looking for the culprit: Case report and review of the literature]. / Hypercalcémie sévère de cause inhabituelle, à la recherche du coupable : cas clinique et revue de la littérature.

INTRODUCTION: Hypercalcemia is not a rare event and can lead to severe consequences. Its main etiologies are primary hyperparathyroidism and neoplasic conditions. The iatrogenic etiology by vitamin D intoxication is more rarely found. CASE PRESENTATION: A 76-year-old finish woman comes to the emergency room for chest pain. Her medical history is impossible to specify due to the language barrier and initial confusion. She has severe hypercalcaemia (4.14mmol/L), renal insufficiency, cardiac arrhythmia later complicated by an ischemic cardiac episode. Clinic and biologic examinations initially guided the research towards a hematological and neoplasic pathology. The iatrogenic etiology will be permitted by the contribution of details on its medical history and treatment learnt secondly. She was treated for post-surgical hypoparathyroidism by dihydrotachysterol, a vitamin D derivative. The cessation of substitution, treatment with hydration and biphosphonates allowed the rapid correction of hypercalcemia. DISCUSSION: Dihydrotachysterol intoxication is a rare etiology of hypercalcemia. Because of the longer half-life of this molecule, the risk of hypercalcemia seems to be greater than with other vitamin D derivatives. This molecule, withdrawn from the French market in 1982, is not detected by the dosage of 25 and 1.25 OH vitamin D. CONCLUSION: We report an original case of intoxication by dihydrotachysterol. The risk of hypercalcemia encountered with this molecule must be known. The close medical follow-up recommended in case of hypoparathyroidism seems to be particularly necessary in case of supplementation by this molecule.

[Hypercalcemia and inactive mutation of CYP24A1. Case-study and literature review]. / Hypercalcémie par mutation inactivatrice du CYP24A1. Étude d'un cas et revue de la littérature.

We present the case of a family whose members have high levels of serum calcium (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187 G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the circulating calcitriol, its tissue concentration and its biological effects. Transmission is recessive. The estimated prevalence of stones in the affected subjects is estimated between 10 and 15%. The loss of peripheral catabolism of vitamin D metabolites in patients with an inactivating mutation of CYP24A1 is responsible for persistent high levels of 1,25-dihydroxyvitamin D especially after sun exposure and a charge of native vitamin D. Although there are currently no recommendations (French review) on this subject, this disease should be suspected in association with recurrent calcium stones with nephrocalcinosis, and a calcitriol-dependent hypercalcaemia with adapted low parathyroid hormone levels. Resistance to corticosteroid therapy distinguishes it from other calcitriol-dependent hypercalcemia. A ratio of 25-hydroxyvitamin D/24.25 hydroxyvitamin D>50, is in favor of hypercalcemia with vitamin D deficiency 24-hydroxylase. Genetic analysis of CYP24A1 should be performed at the second step. The current therapeutic management includes the restriction native vitamin D supplementation and the limitation of sun exposure. Biological monitoring will be based on serum calcium control and modulation of parathyroid hormone concentrations.

[Endocrine causes of delirium]. / Endokrine Ursachen eines akuten Delirs.

Delirium is common in hospitalized patients and apart from well known vascular, infectious and toxic causes there are many endocrine diseases which may also present as an acute confusional state. The review provides an overview of the different endocrine etiologies of delirium and the prompt diagnosis and treatment.

Parathyroid carcinoma: Challenges in diagnosis and treatment.

Parathyroid carcinoma is a malignant neoplasm affecting 0.5 to 5.0% of all patients suffering from primary hyperparathyroidism. This cancer continues to cause challenges for diagnosis and treatment because of its rarity, overlapping features with benign parathyroid disease, and lack of distinct characteristics. The third/second generation PTH assay ratio provides valuable information to distinguish between benign parathyroid disease and parathyroid carcinoma. An abnormal ratio (>1) could indicate a high suspicion regarding carcinoma and metastatic disease. Early en bloc surgical resection of the primary tumour with clear margins remains the best curative treatment. Although prolonged survival is possible with recurrent or metastatic disease, cure is rarely achievable. The efficacy of classical adjuvant therapies, such as radiotherapy and chemotherapy, in management of persistent, recurrent, or metastatic disease has been disappointing. In metastatic disease the goal of therapeutic support is to control the PTH-driven hypercalcemia that represents the primary cause of mortality. Calcimimetics, which are allosteric modulators of the calcium sensing receptor, have a sustained effect in lowering serum calcium levels. Bone anti-resorptive therapy, like intravenous bisphosphonates (pamidronate and zolendronate), or more recently denosumab (fully human monoclonal antibody with high affinity to bind RANK ligand) might be temporarily useful. In a small number of cases treated with anti-PTH immunotherapy, inducing anti-PTH antibodies, promising results have been seen with clinical improvements and decrease of calcemia. In one case metastasis shrinkage has been observed.

Asymptomatic and mild primary hyperparathyroidism.

Primary hyperparathyroidism is common, with epidemiological studies suggesting it may effect up to 1% of the population, and up to 3% of post-menopausal females. Many cases are diagnosed incidentally on routine blood sampling, with the majority of patients being seemingly asymptomatic at diagnosis, and often having mild hypercalcaemia of <2.85mmol/L. Individuals with this so-called mild or asymptomatic primary hyperparathyroidism may however have undiagnosed complications, along with subtle neuropsychological symptoms, and possibly increased cardiovascular risk. Revised international guidelines suggest a more proactive approach to screening for vertebral fractures and renal stones, although the thresholds for recommending definitive surgical management with parathyroidectomy remain similar. The natural history of mild primary hyperparathyroidism will be reviewed, with particular reference to the Parathyroid Epidemiology and Audit Research Study (PEARS), which has used population level data from Tayside, Scotland (UK), along with recent data describing an association with cardiovascular disease. Results of intervention studies, including randomised controlled trials, will also be discussed.