Familial hypocalciuric hypercalcemia as a differential diagnosis of primary hyperparathyroidism with negative images

Introduction. Familial hypocalciuric hypercalcemia is a rare inherited calcium metabolism disorder in which an alteration of the parathyroid hormone secretion set-point causes hypercalcemia with relative hypocalciuria. Some data suggest that its prevalence is around 74.1 per 100,000 inhabitants. Often, patients are asymptomatic. However, they can develop mild symptoms and an overactive parathyroid adenoma, its main differential diagnosis. The objective was to describe a patient’s case and highlight the importance of clinical suspicion and diagnosis to avoid unnecessary surgical neck explorations for parathyroid adenomas. Case report. This is the case of a 40-year-old man with a biochemical profile compatible with primary hyperparathyroidism with anatomical and functional images negative for adenoma and a calcium/creatinine clearance ratio below 0.001, considering familial hypocalciuric hypercalcemia. Genetic studies evidence a mutation in the calcium sensor receptor gene and confirm the diagnosis. Discussion. Familial hypocalciuric hypercalcemia’s main differential diagnosis is an overactive parathyroid adenoma. For both, mild or no symptoms may be present; serum calcium exceeds the upper limit, and parathormone is more than 25pg/ml. The calcium/creatinine clearance ratio should be used to differentiate one from the other and avoid unnecessary surgical neck explorations. Besides the lack of information on this topic, evidence supports the use of calcimimetics to treat symptomatic hypercalcemia. Conclusions. Patients with mild hypercalcemia with parathyroid hormone readings above 25pg/ml and a calcium/creatinine clearance ratio below 0.001, or patients with primary hyperparathyroidism with negative imaging, should not undergo surgical neck explorations. In these cases, familial hypocalciuric hypercalcemia is a reliable diagnosis; Cinacalcet may be administered in cases of symptomatic hypercalcemia.

The crosstalk between gut microbiota, intestinal immunological niche and visceral adipose tissue as a new model for the pathogenesis of metabolic and inflammatory diseases: the paradigm of type 2 diabetes mellitus

Gut microbiota (GM) comprises more than one thousand microorganisms between bacterial species, viruses, fungi, and protozoa, and represents the main actor of a wide net of molecular interactions, involving, among others, the endocrine system, immune responses, and metabolism. GM influences many endocrine functions such as adrenal steroidogenesis, thyroid function, sexual hormones, IGF-1 pathway and peptides produced in gastrointestinal system. It is fundamental in glycaemic control and obesity, while also exerting an important function in modulating the immune system and associated inflammatory disease. The result of this crosstalk in gut mucosa is the formation of the intestinal immunological niche. Visceral adipose tissue (VAT) produces about 600 different peptides, it is involved in lipid and glucose metabolism and in some immune reactions through several adipokines. GM and VAT interact in a bidirectional fashion: while gut dysbiosis can modify VAT adipokines and hormone secretion, VAT hyperplasia modifies GM composition. Acquired or genetic factors leading to gut dysbiosis or increasing VAT (i.e., Western diet) induce a proinflammatory condition, which plays a pivotal role in the development of dysmetabolic and immunologic conditions, such as diabetes mellitus. Diabetes is clearly associated with specific patterns of GM alterations, with an abundance or reduction of GM species involved in controlling mucosal barrier status, glycaemic levels and exerting a pro- or anti-inflammatory activity. All these factors could explain the higher incidence of several inflammatory conditions in Western countries; furthermore, besides the specific alterations observed in diabetes, this paradigm could represent a common pathway acting in many metabolic conditions and could pave the way to a new, interesting therapeutic approach.

The Hydrogen Storage Nanomaterial MgH2 Improves Irradiation-induced Male Fertility Impairment by Suppressing Oxidative Stress

ObjectiveThis study aimed to reveal the protective effect of hydrogen storage nanomaterial MgH2 on radiation-induced male fertility impairment.MethodsThe characterization of MgH2 were analyzed by scanning electron microscopy (SEM) and particle size analyzer. The safety of MgH2 were evaluated in vivo and in vitro. The radioprotective effect of MgH2 on the reproductive system were analyzed in mice, including sperm quality, genetic effect, spermatogenesis, and hormone secretion. ESR, flow cytometry and western blotting assay were used to reveal the underlying mechanisms.ResultsMgH2 had an irregular spherical morphology and a particle size of approximately 463.2 nm, and the content of Mg reached 71.46%. MgH2 was safe and nontoxic in mice and cells. After irradiation, MgH2 treatment significantly protected testicular structure, increased sperm density, improved sperm motility, reduced deformity rates, and reduced the genetic toxicity. Particularly, the sperm motility were consistent with those in MH mice and human semen samples. Furthermore, MgH2 treatment could maintain hormone secretion and testicular spermatogenesis, especially the generation of Sertoli cells, spermatogonia and round sperm cells. In vitro, MgH2 eliminated the [·OH], suppressed the irradiation-induced increase in ROS production, and effectively alleviated the increase in MDA contents. Moreover, MgH2 significantly ameliorated apoptosis in testes and cells and reversed the G2/M phase cell cycle arrest induced by irradiation. In addition, MgH2 inhibited the activation of radiation-induced inflammation and pyroptosis.ConclusionMgH2 improved irradiation-induced male fertility impairment by eliminating hydroxyl free radicals.

Divergent Effect of Central Incretin Receptors Inhibition in a Rat Model of Sporadic Alzheimer’s Disease

The incretin system is an emerging new field that might provide valuable contributions to the research of both the pathophysiology and therapeutic strategies in the treatment of diabetes, obesity, and neurodegenerative disorders. This study aimed to explore the roles of central glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) on cell metabolism and energy in the brain, as well as on the levels of these incretins, insulin, and glucose via inhibition of the central incretin receptors following intracerebroventricular administration of the respective antagonists in healthy rats and a streptozotocin-induced rat model of sporadic Alzheimer’s disease (sAD). Chemical ablation of the central GIP receptor (GIPR) or GLP-1 receptor (GLP-1R) in healthy and diseased animals indicated a region-dependent role of incretins in brain cell energy and metabolism and central incretin-dependent modulation of peripheral hormone secretion, markedly after GIPR inhibition, as well as a dysregulation of the GLP-1 system in experimental sAD.

A retroperitoneal bronchogenic cyst clinically mimicking an adrenal mass: three case reports and a literature review

Bronchogenic cysts are a congenital primitive foregut-derived developmental malformation, generally occurring in the posterior mediastinum. Their development in the retroperitoneum is extremely rare. Imaging techniques, such as multidetector computed tomography (MDCT), are typically effective in the detection of these lesions. Here, we describe three cases of a retroperitoneal cyst presenting as a para-adrenal mass. Only one boy presented with abdominal pain, and the other two showed no clinical symptoms. Endocrinological evaluation of all three cases was performed, and no adrenal hormone secretion was detected. All three cases were misdiagnosed preoperatively. Each patient underwent surgery, and one symptomatic patient became asymptomatic after surgery. Pathologic examination confirmed all three masses as bronchogenic cysts. The three cases showed some similar MDCT imaging features, including a complete adrenal structure, a cystic or solid mass in the adrenal region, and no obvious enhancement. Therefore, bronchogenic cysts should be considered in the differential diagnosis of retroperitoneal masses, even though accurate preoperative diagnosis remains difficult. A contrast-enhanced MDCT scan may be useful for differentiating hyper-attenuated cysts from other soft tissue masses.

Sodium and water perturbations in patients who had an acute stroke: clinical relevance and management strategies for the neurologist

Sodium and water perturbations, manifesting as hyponatraemia and hypernatraemia, are common in patients who had an acute stroke, and are associated with worse outcomes and increased mortality. Other non-stroke-related causes of sodium and water perturbations in these patients include underlying comorbidities and concomitant medications. Additionally, hospitalised patients who had an acute stroke may receive excessive intravenous hypotonic solutions, have poor fluid intake due to impaired neurocognition and consciousness, may develop sepsis or are administered drugs (eg, mannitol); factors that can further alter serum sodium levels. Sodium and water perturbations can also be exacerbated by the development of endocrine consequences after an acute stroke, including secondary adrenal insufficiency, syndrome of inappropriate antidiuretic hormone secretion and diabetes insipidus. Recently, COVID-19 infection has been reported to increase the risk of development of sodium and water perturbations that may further worsen the outcomes of patients who had an acute stroke. Because there are currently no accepted consensus guidelines on the management of sodium and water perturbations in patients who had an acute stroke, we conducted a systematic review of the literature published in English and in peer-reviewed journals between January 2000 and December 2020, according to PRISMA guidelines, to assess on the current knowledge and clinical practices of this condition. In this review, we discuss the signs and symptoms of hyponatraemia and hypernatraemia, the pathogenesis of hyponatraemia and hypernatraemia, their clinical relevance, and we provide our recommendations for effective treatment strategies for the neurologist in the management of sodium and water perturbations in commonly encountered aetiologies of patients who had an acute stroke.