Dal Pensiero selvaggio al Sistema di Politica positiva: riproporre tutto Lévi-Strauss per rileggere tutto Comte.

Nell'ultima edizione del Pensiero selvaggio, purtroppo a tutt'oggi indisponibile in lingua italiana, Lévi-Strauss rilegge Comte recuperando in particolare il pensiero espresso da quest'ultimo nella sua ultima grande opera, il Sistema di politica positiva. Il Comte teorico del feticismo diventa, nella "rilettura" di Lévi-Strauss, l'antesignano della sua antropologia strutturale: il feticismo, che nell'ultimo Comte rivela una particolare affinità col positivismo, è ben lungi dall'essere uno stadio primitivo destinato agli archivi dell'umanità; esso rivive anzi nel presente, così come il "pensiero selvaggio" del grande antropologo francese

Occurrence of malignant neoplasia in patients with primary hyperparathyroidism

Introduction The association between primary hyperparathyroidism (1HPT) and cancer is debated. The present study was aimed to investigate the occurrence of neoplasia in 1HPT. Patients and methods All consecutive patients (n = 1750) referred to our \u201cOsteoporosis and Metabolic Disease\u201d outpatients clinic for osteoporosis or hypercalcemia were eligible for the study. The exclusion criteria were: the finding of osteoporosis and/or altered calcium-phosphorous metabolism in the context of investigations for malignancy, the presence of diseases known to influence the cancer risk and the heavy smoking habit. Eventually, 1606 patients (1407 females, 199 males) were enrolled. In all patients calcium-phosphorous metabolism, PTH and vitamin D levels were measured and the occurrence of cancer during the 10 years prior the study inclusion was recorded. Results One-hundred-sixty-three patients had 1HPT while 1443 had not. Patients with and without 1HPT were comparable for age and gender. In 1HPT patients the occurrence of all, breast, kidney and skin cancer was significantly higher (21.5%, 12.2%, 2.5%, 1.8%, respectively) than in patients without 1HPT (12.4%, 6.9%, 0.3%, 0.3%, p < 0.05 for all comparisons). The 1HPT presence was significantly associated with the occurrence of all neoplasia and of breast, skin and kidney neoplasia (odds ratio, 95% confidence interval, p value: 1.93, 1.27\u20132.92, 0.002; 1.93, 1.11\u20133.35, 0.002; 9.18, 2.16\u201338.8, 0.003; 8.23, 1.71\u201339.5, 0.008, respectively), after adjusting for age, gender (as appropriate), smoking habit and vitamin D levels. Conclusion During the 10 years prior the diagnosis of 1HPT, the occurrence of all, breast, skin and kidney neoplasia is increased

A novel mutation in calcium-sensing receptor gene associated to hypercalcemia and hypercalciuria.

Background: Familial Hyperparathyroidism (HPT) and Familial benign Hypocalciuric Hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. FHH has been demonstrated to be caused by inactivating mutations of calcium-sensing receptor (CaSR) gene, involved in PTH regulation as well as in renal calcium excretion.Case presentation: In two individuals, father and son, we found a novel heterozygous mutation in CaSR gene. The hypercalcemia was present only in father, which, by contrast to the classic form of FHH showed hypercalciuria (from 300 to 600 mg/24 h in different evaluations) and a Calcium/Creatinine ratio of 0.031, instead of low or normal calciuria (<0.01 typical finding in FHH). His son showed the same mutation in CaSR gene, but no clinical signs or hypercalcemia although serum ionized calcium levels were close to the upper limit of normal values (1.30 mmol/L: normal range: 1.12-1.31 mmol/L). Sequence analysis revealed a point mutation at codon 972 of CaSR gene (chromosome 3q), located within cytoplasmic domain of the CaSR, that changes Threonine with Methionine. The father was treated with Cinacalcet 90 mg/day, with a decrease of total serum calcemia from an average value of 12.2 mg/dl to 10.9 mg/dl.Conclusion: This is a case of a novel inactivating point mutation of CaSR gene that determines an atypical clinical presentation of FHH, characterized by hypercalcemia, hypercalciuria and inadequate normal PTH levels. Functional assay demonstrated that the 972 M variant influenced the maturation of the protein, in terms of the post-translational glycosylation. The impairment of the receptor activity is in keeping with the specific localization of the 972 residue in the C-terminal tail, assigned to the intracellular signalling, that on the basis of the our findings appears to be differently modulated in parathyroid gland and in kidne

Defining non-functioning adrenal adenomas on the basis of the occurrence of hypocortisolism after adrenalectomy

Background In patients with adrenal incidentalomas (AI), there is uncertainty on how to rule out hypercortisolism. The occurrence of post-surgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of a pre-surgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC) and adrenocorticotroph hormone (ACTH) able to predict the absence of PSH in AI patients undergoing surgery. Methods In 60 patients who underwent AI excision, cortisol secretion was assessed by low-dose corticotropin stimulation test or insulin tolerance test, when needed. We searched for the lowest pre-surgical value of F-1mgDST, UFC and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion. Results the lowest values of F-1mgDST, UFC and MSC and the highest value for ACTH in PSH patients were 1.2 \ub5g/dL (33 nmol/L), 10.4 \ub5g/24h (29 nmol/24h), 1.2 \ub5g/dL (33 nmol/L) and 26.9 pg/ml (6 pmol/L), respectively, but only F-1mgDST &lt;1.2 \ub5g/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST &lt;1.2 \ub5g/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome and these subjects tended to have a better metabolic profile than those with F-1mgDST 651.2 \ub5g/dL (33nmol/L) Conclusion in AI patients a F-1mgDST &lt;1.2 \u3bcg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients

Pathophysiology of Mild Hypercortisolism: From the Bench to the Bedside

Mild hypercortisolism is defined as biochemical evidence of abnormal cortisol secretion without the classical detectable manifestations of overt Cushing’s syndrome and, above all, lacking catabolic characteristics such as central muscle weakness, adipose tissue redistribution, skin fragility and unusual infections. Mild hypercortisolism is frequently discovered in patients with adrenal incidentalomas, with a prevalence ranging between 5 and 50%. This high variability is mainly due to the different criteria used for defining this condition. This subtle cortisol excess has also been described in patients with incidentally discovered pituitary tumors with an estimated prevalence of 5%. To date, the mechanisms responsible for the pathogenesis of mild hypercortisolism of pituitary origin are still not well clarified. At variance, recent advances have been made in understanding the genetic background of bilateral and unilateral adrenal adenomas causing mild hypercortisolism. Some recent data suggest that the clinical effects of glucocorticoid (GC) exposure on peripheral tissues are determined not only by the amount of the adrenal GC production but also by the peripheral GC metabolism and by the GC sensitivity. Indeed, in subjects with normal cortisol secretion, the combined estimate of cortisol secretion, cortisone-to-cortisol peripheral activation by the 11 beta-hydroxysteroid dehydrogenase enzyme and GC receptor sensitizing variants have been suggested to be associated with the presence of hypertension, diabetes and bone fragility, which are three well-known consequences of hypercortisolism. This review focuses on the pathophysiologic mechanism underlying both the different sources of mild hypercortisolism and their clinical consequences (bone fragility, arterial hypertension, subclinical atherosclerosis, cardiovascular remodeling, dyslipidemia, glucose metabolism impairment, visceral adiposity, infections, muscle damage, mood disorders and coagulation). © 2022 by the authors. Licensee MDPI, Basel, Switzerland

Management of osteoporosis in men: A narrative review

Male osteoporosis is a still largely underdiagnosed pathological condition. As a conse-quence, bone fragility in men remains undertreated mainly due to the low screening frequency and to controversies in the bone mineral density (BMD) testing standards. Up to the 40% of overall osteo-porotic fractures affect men, in spite of the fact that women have a significant higher prevalence of osteoporosis. In addition, in males, hip fractures are associated with increased morbidity and mortality as compared to women. Importantly, male fractures occur about 10 years later in life than women, and, therefore, due to the advanced age, men may have more comorbidities and, consequently, their mortality is about twice the rate in women. Gender differences, which begin during puberty, lead to wider bones in males as compared with females. In men, follicle-stimulating hormones, testosterone, estrogens, and sex hormone-binding levels, together with genetic factors, interact in determining the peak of bone mass, BMD maintenance, and lifetime decrease. As compared with women, men are more frequently affected by secondary osteoporosis. Therefore, in all osteoporotic men, a complete clinical history should be collected and a careful physical examination should be done, in order to find clues of a possible underlying diseases and, ultimately, to guide laboratory testing. Currently, the pharmacological therapy of male osteoporosis includes aminobisphosphonates, denosumab, and teriparatide. Hypogonadal patients may be treated with testosterone replacement therapy. Given that the fractures related to mortality are higher in men than in women, treating male subjects with osteoporosis is of the utmost importance in clinical practice, as it may impact on mortality even more than in women

When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis

Objective: To investigate whether the available literature helps to identify the characteristics of patients with type 2 diabetes (T2D) more frequently associated with hidden hypercortisolism (HidHyCo). Methods: A meta-analysis was performed using studies that assessed both the prevalence of HidHyCo in patients with T2D and the characteristics of these patients with and without HidHyCo. The DerSimonian and Laird (DSL) and Hartung-Knapp-Sidik-Jonkman (HKSJ) methods were utilized. Results: Among the 18 available studies, 6 provided the necessary data. The association between HidHyCo and advanced T2D (based on the patients’ description given in each study in the presence of microvascular/macrovascular complications or insulin treatment plus hypertension or hypertension treated with 2 or more drugs), hypertension, insulin treatment, and dyslipidemia was reported in 5 (2184 patients), 6 (2283 patients), 3 (1440 patients), and 3 (987 patients) studies, respectively. HidHyCo was associated with advanced T2D as assessed by both the DSL (odds ratio [OR], 3.4; 95% confidence interval [95% CI], 2.12-5.67) and HKSJ (OR, 3.60; 95% CI, 2.03-6.41) methods and with the prevalence of hypertension or insulin treatment as assessed by the DSL method (OR, 1.92; 95% CI, 1.05-3.50 and OR, 2.29; 95% CI, 1.07-4.91, respectively) but not as assessed by the HKSJ method. Conclusion: Patients with advanced T2D have a higher prevalence of HidHyCo. These data inform about the selection of patients with T2D for HidHyCo screening

Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders

Objective: The aim of this study was to analyze variants of the gene glial cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma. Design: We characterized 2 families with hypoparathyroidism and 19 with FIHP in which we examined the mechanism of action of GCM2 variants. Methods: Leukocyte DNA of hypoparathyroid individuals was Sanger sequenced for CASR, PTH, GNA11 and GCM2 mutations. DNA of hyperparathyroid individuals underwent MEN1, CDKN1B, CDC73, CASR, RET and GCM2 sequencing. The actions of identified GCM2 variants were evaluated by in vitro functional analyses. Results: A novel homozygous p.R67C GCM2 mutation which failed to stimulate transcriptional activity in a luciferase assay was identified in affected members of two hypoparathyroid families. Oligonucleotide pull-down assay and in silico structural modeling indicated that this mutant had lost the ability to bind the consensus GCM recognition sequence of DNA. Two novel (p.I383M and p.T386S) and one previously reported (p.Y394S) heterozygous GCM2 variants that lie within a C-terminal conserved inhibitory domain were identified in three affected individuals of the hyperparathyroid families. One family member, heterozygous for p.I138M, had parathyroid carcinoma (PC), and a heterozygous p.V382M variant was found in another patient affected by sporadic PC. These variants exerted significantly enhanced in vitro transcriptional activity, including increased stimulation of the PTH promoter. Conclusions: We provide evidence that two novel GCM2 R67C inactivating mutations with an inability to bind DNA are causative of hypoparathyroidism. Additionally, we provide evidence that two novel GCM2 variants increased transactivation of the PTH promoter in vitro and are associated with FIHP. Furthermore, our studies suggest that activating GCM2 variants may contribute to facilitating more aggressive parathyroid disease

Large deletion at the CDC73 gene locus and search for predictive markers of the presence of a CDC73 genetic lesion

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the CDC73 gene: it has been suggested that early onset of the disease and high Ca2+ levels may predict the presence of a CDC73 mutation. We searched for large deletions at the CDC73 locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a CDC73 gene mutation, clinical/histological diagnosis, age at onset, Ca2+, PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a CDC73 gene mutation. A novel genomic deletion of the first 10 exons of the CDC73 gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a CDC73 mutation in subjects with age at the onset &lt; 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca2+ levels &lt;13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1, p &lt; 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset &lt; 41.5 ys and Ca2+ &gt; 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion