The endocrine role of estrogens on human male skeleton

Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men

Genetic screening for infertility: When should it be done?

Depending on the clinical findings, the infertile male patient needs genetic evaluation. Karyotype analysis and Y-chromosomal microdeletion screening should be performed in patients with azoospermia or severe oligozoospermia in order to rule out structural chromosomal abnormalities, Klinefelter syndrome and Y chromosome microdeletions. Infertile patients with obstructive azoospermia need cystic fibrosis transmembrane receptor gene screening, while in patients with hypogonadotropic hypogonadism mutation screening may be performed according to clinical features. All genetic analyses should be accompanied by expert counseling by a clinical genetist both in male and female patients. Primary amenorrhea should be investigated by karyotype analysis and selected mutation screening according to the patient's clinical features. Karyotype analyses and FMR1 gene screening is recommended in cases of POF. At present the infertility of patients with POF cannot be restored if the diagnosis is made after complete follicular depletion, but in some cases, early diagnosis by genetic investigation may instead lead to the advice of early conception or oocyte harvesting and preservation. In addition, the accumulation and annotation of array comparative genomic hybridization data might, in the near future, lead to the identification of pathogenetic copy number variations and genes involved in POF. Karyotype analysis of both partners is recommended in all couples with recurrent pregnancy loss. No routine genetic test can be recommended so far in patients with PCOS

Serum calcium to phosphorous ratio (Ca/P) as a simple, inexpensive screening tool in the diagnosis of primary hyperparathyroidism (PHPT)

Background PHPT is often overlooked/underdiagnosed. Several strategies (biochemical markers alone or combined in complex algorithms) have been investigated to easily diagnose/screen PHPT, but PHPT diagnosis remains challenging at present, especially in asymptomatic patients. As serum calcium (Ca) and phosphorous (P) are inversely related in PHPT, the Ca/P ratio could be a good candidate tool for PHPT diagnosis. Surprisingly, no literature data on Ca/P ratio are available, despite they are very simple biochemical measurements largely available in any clinical lab setting. Aim To investigate the Ca/P ratio diagnostic value in the diagnosis of PHPT. Methods Data retrospectively obtained from review charts of 97 patients with documented PHPT (69 females; 28 males) [16 (17%) with severe hypercalcemia (O12 mg/dl); 44 (45%) mild hypercalcemia, 36 (38%) normocalcemic PHPT (NCHPT)] were compared with those of 96 controls (C) (44 females; 52 males). Exclusion criteria: age !18 years, severe chronic diseases, cancer, bone metabolic diseases, use of medications affecting serum Ca. Biochemical measurements: PTH, Vitamin D, serum Ca, P, albumin, and creatinine. Normal ranges: PTH (15–88 pg/ml), Ca (8.5–11 mg/dl), P (2.5–5.1 mg/dl). SPSS 19.0 and SigmaPlot 11.0 were used for statistics (group comparisons, ROC curves, cutoffs performance). Results Ca and PTH were significantly higher in PHPT [(Ca median:11; min-max:9.4– 15.5); (PTH 135.2; 57.6–1748)] than C [(Ca 9.4; 8.3–10.2); (PTH 32.1; 14–106.1) (P!0.0001). P was significantly lower in PHPT (2.4; 1.4–3.9) than in C (3.5; 2.1– 4.5) (P!0.0001). Ca/P ratio was significantly higher in PHPT than in C. ROC curves analyses identified a cutoff of 3.5 for both Ca/P ratio and Ca/P ratio obtained by using albumin corrected-Ca. The sensitivity and specificity were 86 and 87%, respectively for Ca/P ratio and 89 and 93%, respectively for corrected Ca/P ratio (P!0.0001). The diagnostic value of Ca/P ratio performed better than PTH and Ca used alone or in combination. Conclusions Ca/P ratio is a valuable highly sensitive, highly specific tool for the diagnosis of PHPT. Since Ca/P is simple to obtain, easily accessible in every clinical and lab setting worldwide, and inexpensive even when used in large sample size of patients, this diagnostic tool could be useful for screening PHPT, especially in patients accessing emergency rooms or in the general practitioner setting

Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms

In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multi-target tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by regulatory agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in depth review on the studies published on the following MTKIs in neuroendocrine tumours: axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on clinical trial registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastro-entero-pancreatic and lung NENs identifies in vitro and in vivo studies which demonstrate anti-tumour activity of diverse MTKIs on neuroendocrine cells and tumours. Moreover, for the first time in the literature, we report an updated view concerning the upcoming clinical trials in this field: presently, phase I, II, and III clinical trials are ongoing and will include, overall, a staggering 1667 patients. This fervid activity underlines the increasing interest of the scientific community in the use of emerging MTKIs in NEN treatment

Espressione di miRNA-146a nel carcinoma follicolare della tiroide e correlazione con istotipo e stadiazione clinica

This study investigates the relationship among miRNA-146a and clinical and histological correlates in follicular thyroid cance

Pre-miR146a expression in follicular carcinomas of the thyroid

INTRODUCTION: Micro-RNA, a new class of small, non-coding RNAs, have been shown to be deregulated in several human carcinomas. In particular, SNP rs2910164 in pre-miR146a appears to be correlated with papillary thyroid carcinoma and may be involved in its genetic predisposition. Since data on follicular thyroid carcinomas (FTC) are lacking, we evaluated the involvement of SNP rs2910164 in FTC. METHODS: Thirty-nine cases of FTC and 20 follicular adenomas, defined according to WHO criteria, were selected. DNA and RNA were extracted from formalin-fixed paraffin-embedded blocks of both neoplastic and non-neoplastic areas. The DNA region of pre-miR146a, containing SNP rs2910164, was sequenced. Total RNA including miRNAs was used for stem-loop RT reactions, and applying a standard TaqMan PCR kit protocol for real-time PCR. Wilcoxon signed-rank test and Friedman test were used for statistical analyses. RESULTS: In 31% of FTC, the G allele was observed in neoplastic tissues, compared with the non-neoplastic areas (p < 0.05), whereas the CC phenotype was completely absent in tumours. Moreover, the expression of pre-miR146a was found to be significantly down-regulated in neoplastic tissues from FTC cases (p = 0.043), although no significant differences were seen in follicular thyroid adenomas. DISCUSSION: The expression profile of pre-miR146a can be correlated with FTC tumourigenesis. The G allele in SNP rs2910164 appears to be correlated with the transition from normal to neoplastic tissue. The GG and GC alleles appear to be associated with an increased risk for FTC, while the CC allele seems to play a protective role

Exploring the Possible Prognostic Role of B-Lymphocyte Stimulator (BLyS) in a Large Series of Patients with Neuroendocrine Tumors

BLyS (B-Lymphocyte stimulator) is over-expressed in several tumoral settings, with direct or indirect effects on neoplastic proliferation and possibly representing a therapeutic target. In this study we explored the role of BLyS in a large population of patients with neuroendocrine tumors (NETs)

Mazabraud's Syndrome: A Case Report And Up-To-Date Literature Review

Mazabraud's syndrome is a rare form of bone fibrous dysplasia associated with intramuscular myxomas. Fibrous dysplasia, is generally localized to pelvis and femur and it results in a fragile bone with deformities, pain, pathological fractures and functional impairment. Intramuscular myxomas, are rare benign mesenchymal neoplasms that exceptionally may evolve to malignant forms

New insights on follicular thyroid carcinoma: the role of pre-mir-146a

Role of pre-mir-146a on follicular thyroid cance