Minerva endocrinology最新文献

Introduction: Male fertility relies on a complex physiology that may be negatively influenced by lifestyle, diet, and environment. The beneficial effect of nutraceuticals on male fertility is a debated claim. The aim of this study was to assess if the positive effect of nutraceuticals can counteract the negative effects of the environment on male fertility.

Evidence acquisition: PubMed^®/MEDLINE^®, Embase and Cochrane Database were searched (September-October 2023), along with crosschecking of references and search for ongoing studies of the effects of the environment and nutraceuticals on male fertility, in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Evidence synthesis: Several environmental factors such as microplastic and other endocrine-disrupting chemicals and climate changes may affect the sperm quality in terms of reduction of sperm count number, mobility and altered morphology and thereby reduce male fertility. On the other hand, new evidence demonstrates that a balanced diet rich in antioxidants and essential nutrients, together with minimized exposure to environmental toxins, may improve male fertility and reproductive health. Several nutraceutical compounds proved a protective role against negative environmental effects on male fertility.

Conclusions: Available evidence confirms that the environment may negatively impact male fertility, and this impact is estimated to rise in the forthcoming years. On the other hand, new data indicate that nutraceuticals may have a protective role against the negative impact of environmental factors on male fertility. The need for future studies to monitor and explore these aspects of men's health cannot be underestimated.

Introduction: Several data demonstrated that chemical pollutants can be endocrine disruptors and they have an important role in tumorigenic processes. It has been shown that pollution exposure can affect pituitary cells' function and biology, indeed an increased prevalence of acromegaly has been reported in highly polluted areas.

Evidence acquisition: One transcription factor that has a role in both carcinogenesis and in xenobiotics' detoxification is the aryl hydrocarbon receptor (AHR). Its deregulation could have a pivotal role in pituitary tumors, especially in GH-secreting pituitary tumors. Environmental chemicals affect the expression and function of ncRNAs (miRNA, lncRNA and circRNA) through different mechanisms.

Evidence synthesis: However, to date, few data on the role of the environmental pollutants in the clinical expression and pathogenesis of GH-secreting pituitary tumors are available.

Conclusions: This article presents a summary of the AHR signaling pathways that are triggered by various ligands and emphasizes the significant distinctions between the potential biological and toxicological effects of AHR gene activation. We also deepen the functions of ncRNAs and acromegaly and provide current data on their regulation by the AHR. Overall, more studies are still needed to fully understand the dynamic interplay between the AHR signaling pathway and ncRNAs in GH-secreting pituitary adenomas.

Background: The clinical management of repeatedly non-diagnostic thyroid nodules (RNDNs) via fine needle aspiration cytology (FNAc) is a matter of debate because current recommendations and clinical practice are not based on high-quality evidence. Our purpose was to characterize RNDNs and evaluate their clinical management in our centers.

Methods: This retrospective observational study included 319 consecutive patients who underwent ultrasound (US-)guided FNAc in two Italian academic hospitals between 2016 and 2020 and had previous cytology non-diagnostic result (TIR1). Clinical management and anamnestic data were retrieved, and the cytological specimens and US exams were double-blindly reviewed by two pathologists and endocrinologists.

Results: The risk of RNDNs was significantly greater in hypoechogenic nodules (Odds Ratio [OR]=1.727, 95% confidence Interval [CI]: 1.090-2.735, P=0.02) and lower in nodules that had been recognized less than 10 years before (OR=0.349, 95% CI: 0.153-0.796, P=0.01). Clinicians chose to directly perform surgery on multinodular, intermediate-risk nodules (as per AACE/AME guidelines and EUTIRADS class 4), while larger (P<0.0001) and uninodular (P=0.03) lesions were further investigated with a third FNAc. Only 16 RNDNs were sent to surgery. Twelve nodules turned out to be benign goiters with a high rate of fibrosis, while only 3 were definitively malignant. However, retrospectively, all the malignant ones exhibited higher-risk ultrasound features and had an undetermined result (TIR3B) at the third cytological evaluation.

Conclusions: In a real-life context, RNDNs exhibited a very low rate of malignancy and were mostly long-known goiters with regressive changes, as suggested by a hypoechoic pattern. Consequently, a clinical-US surveillance approach could be cautiously hypothesized, while greater attention could be given to larger and higher-US-risk (both as EUTIRADS 4-5 and AACE/AME intermediate- and high-risk classes) nodules.

Aggressive pituitary tumors are a subset of pituitary neoplasms, characterized by unusually fast growth rate, invasiveness and overall resistance to optimized standard treatment. When metastases are present, the term pituitary carcinoma is employed. After failure of standard treatments, current guidelines recommend first-line temozolomide monotherapy. However, a significant number of patients do not respond to temozolomide, or experience disease progression following its discontinuation; in these latter cases, re-challenge with temozolomide is generally advised, although the reported outcomes have been less satisfactory. Although no alternative therapies have been formally recommended after temozolomide failure, growing evidence regarding potential second- or third-line therapeutic strategies has emerged. In the present work, we reviewed the available evidence published up to April 2023 involving the most relevant therapies employed so far, namely immune checkpoint inhibitors, bevacizumab, peptide radionuclide receptor therapy, tyrosine kinase inhibitors and mTOR inhibitors. For each treatment, we report efficacy and safety outcomes, along with data regarding potential predictors of response. Overall, immune checkpoint inhibitors and bevacizumab are showing the most promise as therapeutic options after temozolomide failure. The former showed better responses in pituitary carcinomas. Peptide radionuclide receptor therapy has also showed some efficacy in these tumors, while tyrosine kinase inhibitors and mTOR inhibitors have exhibited so far limited or no efficacy. Further studies, as well as an individualized, patient-tailored approach, are clearly needed. In addition, we report an unpublished case of a silent corticotroph pituitary carcinoma that progressed under dual immunotherapy, and then showed stable disease under a combination of lomustine and bevacizumab.

Background: Prolactin (PRL) is a peptide hormone secreted by the anterior pituitary that provides lactation during the postpartum period. The causes of hyperprolactinemia are pituitary tumors, medications, primary hypothyroidism, polycystic ovary syndrome (PCOS), renal failure, idiopathic, and other physiological causes such as pregnancy and lactation. In this study, we aimed to investigate the prevalence of hyperprolactinemia etiologies and the mean/median prolactin levels in different etiologies.

Methods: The patients admitted to our outpatient clinic between January 2009-December 2019 were retrospectively screened from our hospital database with ICD-10 codes. Four hundred patients were included in the study; 69.5% of the patients were women. Their mean age was 43.67±13.42 years, the duration of illness was 7.8±5.6 years. The most frequent causes of hyperprolactinemia were found as follows: 52.5% (N.=210) prolactinoma, 7% (N.=28) gonadotropinoma, 6.5% (N.=26) drug-related, 6.5% (N.=25) PCOS, 5.8% (N.=23) idiopathic, 5% (N.=20) acromegaly, 4.8% (N.=19) nonfunctioning adenoma 2.3% (N.=9) craniopharyngioma. Patients with gonodotropinoma were significantly older, and the patients with PCOS were significantly younger than the patients with hyperprolactinemia due to the other etiologies. Patients with prolactinoma had significantly higher prolactin levels and longer duration of the illness when compared to other etiologies of hyperprolactinemia (168.00* ng/mL [14-23,500] [168]); 8* years (0-39) (5.00) years respectively, *median values, (min-max levels) and (interquartile range), respectively.

Results: There was no significant difference between prolactin levels of other etiologic groups except prolactinoma. Surprisingly, we found PCOS patients with prolactin levels greater than 100 ng/mL and acromegaly or drug-induced hyperprolactinemia with prolactin levels greater than 200 ng/mL. In our study, unlike the literature, macroprolactinemia can be seen alone or together with other pathologies. Except for macroprolactinoma, it is not possible to diagnose according to prolactin level. Similar to the literature, prolactinoma was the most common cause of hyperprolactinemia. The causes of hyperprolactinemia, in order of decreasing frequency, were determined to be gonodotropinoma, drug-related, PCOS, idiopathic, and acromegaly. The range of prolactin detected in PCOS is given as new information. It was found that the pediatric group and the adult group had a similar etiology and PRL level.

Conclusions: A large spectrum of physiologic/pathologic conditions increases the prolactin levels, and prolactin levels may vary from person to person. So, the serum prolactin level alone does not guide a clinical diagnosis or make a differential diagnosis.

Background: We examined different molecular forms of luteinizing hormone (LH) in urine samples taken during periovulatory days with the aim of revealing different forms of LH immunoreactivity (LH-ir) in normally menstruating women.

Methods: Serum and first-morning-voided urine serum samples were obtained from six healthy, 22 to 38 years old, regularly menstruating women during their periovulatory days based on their previous menstrual cycles. The day of the LH surge was determined on the basis of serum LH concentrations and confirmed by an at least two-fold increase in urinary concentrations of intact LH on consecutive days. Different molecular forms of LH-ir were identified by gel filtration of first-morning-voided urine samples obtained from regularly menstruating women on periovulatory days.

Results: Different forms of LH immunoreactivity (LH-ir) were distinguished as intact LH, its free beta-subunit (LHβ), and the core fragment of LHβ (LHβcf) according to their molecular sizes. The latter two are also called non-intact LH. Intact LH was the dominating form on the day before and on the day of LH surge while LHβcf was the major form of LH immunoreactivity after the LH surge for the following 5-7 days. LHβ was detected on the day of the LH surge as well as on the following day.

Conclusions: These results indicate that LH is degraded in the kidneys and excreted as LHβ, and mainly as LHβcf for 7 days following the LH peak.

Macroglossia is an uncommon condition characterized by chronic, painless and abnormal enlargement of the tongue. A multitude of medical conditions can cause macroglossia. Major endocrine and metabolic disorders associated with macroglossia include genetic, congenital and acquired conditions, such as mucopolysaccharidoses; acquired and congenital hypothyroidism and myxedema; transient neonatal diabetes mellitus; acromegaly and amyloidosis. Macroglossia is often associated (~57-60%) with all types of mucopolysaccharidoses, particularly type I (Hurler syndrome) and type II (Hunter syndrome), being a prominent feature of the disorder. It may also occur in patients with acquired and congenital hypothyroidism and myxedema, being a common sign of congenital hypothyroidism with an approximate prevalence of 12-25% at the time of diagnosis. Macroglossia is a predominant oral finding in subjects with transient neonatal diabetes mellitus (~44%), acromegaly (54-69%) and amyloidosis (10-25%), particularly AL amyloidosis (20-40%) whereas is considered a hallmark of the disease. Secondary to macroglossia various disturbances may occur, such as difficulty in speech or eating, orthodontic anomalies or even more serious conditions including upper airway obstruction or obstructive sleep apnea. Until now, no comprehensive review has been conducted focusing on macroglossia in endocrine and metabolic disorders. The objective of this review is to summarize literature on the etiology and epidemiology of macroglossia in major endocrine and metabolic disorders. It highlights key aspects such as pathophysiology, clinical presentation, diagnostic evaluation, management and prognosis of macroglossia in the context of endocrine and metabolic disorders.

Precision, personalized, or individualized medicine in pituitary neuroendocrine tumors (PitNETs) has become a major topic in the last few years. It is based on the use of biomarkers that predictively segregate patients and give answers to clinically relevant questions that help us in the individualization of their management. It allows us to make early diagnosis, predict response to medical treatments, predict surgical outcomes and investigate new targets for therapeutic molecules. So far, substantial progress has been made in this field, although there are still not enough precise tools that can be implemented in clinical practice. One of the main reasons is the excess overlap among clustered patients, with an error probability that is not currently acceptable for clinical practice. This overlap is due to the high heterogeneity of PitNETs, which is too complex to be overcome by the classical biomarker investigation approach. A systems biology approach based on artificial intelligence techniques seems to be able to give answers to each patient individually by building mathematical models through the interaction of multiple factors, including those of omics sciences. Integrated studies of different molecular omics techniques, as well as radiomics and clinical data are necessary to understand the whole system and to finally achieve the key to obtain precise biomarkers and implement personalized medicine. In this review we have focused on describing the current advances in the area of PitNETs based on the omics sciences, that are clearly going to be the new tool for precision medicine.

Background: The dopaminergic agonist cabergoline (CAB) has been used in the pharmacological treatment of Cushing's disease (CD). The effect is attributed to the frequent expression of the dopamine receptor subtype 2 in corticotroph tumors. However, in-vivo studies have demonstrated the normalization of 24-h urinary cortisol (24-h UC) in approximately 30-40% of patients over the long term, mainly after surgical failure. The aim was to evaluate the effect of CAB as monotherapy in the early preoperative period and on the recurrence of CD.

Methods: A single-center retrospective study was conducted in a tertiary referral center. Twenty-one patients with confirmed CD were included. The median age was 32 years (13-70), 86% were female, 10 had microadenomas, and 11 had macroadenomas. They were diagnosed from 1986 to 2016 and used CAB as monotherapy either in the preoperative period (N.=7, CABi) or upon recurrence before any other treatment (N.=14, CABr). A "complete response" was considered 24-h UC normalization and a "partial response" was considered a 24-h UC reduction of >50%. UC was obtained at the last follow-up evaluation. The normalization of late-night salivary cortisol (LNSC) after CAB use was evaluated in most patients, as well as the tumor diameter by pituitary MRI, before and after CAB treatment.

Results: Complete response was achieved in 29% (6/21) of subjects after 14.9±16.4 months of treatment, with an average dose of 2.2±1.0 mg/week. Partial response occurred in 9.5% (2/21). LNSC normalized in 35% (6/17) of patients, and no variation in tumor diameter before and after CAB use was observed (N.=13): 6.8±6.8 vs. 7.2±7.1 mm. There was no normalization of 24-h-UC in the CABi subgroup at the end of the treatment, whereas 43% (6/14) of patients in the CABr subgroup reached complete response. The CABi subgroup was treated for 4.7±1.9 months, and the CABr subgroup was treated for 20.1±18.1 months. Both groups were administered similar doses of CAB (CABi 2.1±0.9 and CABr 2.3±1.1 mg/week). Interestingly, the difference between the subgroups' complete response was evident early on in the three months of treatment: no patients in the CABi subgroup vs. 6/10 (60%) in the CABr subgroup (P=0.035), despite a lower dose in the CABr subgroup (1.1 vs. 1.6; P=0.008). The normalization of LNSC occurred in 20% of the CABi subgroup and in 42% of the CABr subgroup.

Conclusions: The normalization of 24-h UC and LNSC occurred in approximately 30% of all patients, mainly in those who used CAB for the recurrence of CD. Despite the small number of subjects in the CABi subgroup, the absence of hormone control in this subgroup discourages the use of this medication as primary therapy or as a preoperative treatment option.

Background: Craniopharyngioma (CP) is a rare tumor, leading to several post-treatment sequelae which may have significant clinical and social implications, including impaired academic performance or employability.

Methods: We conducted a retrospective study involving CP patients followed at our center between 1986 and 2020. Data on demographics, clinical, imaging, and treatment characteristics were collected from the clinical records.

Results: There were 33 patients (current mean age of 49.8±18.7 years), being 22 diagnosed in adulthood. The average follow-up duration was 16.03±9.3 years. Twelve patients were treated with surgery alone, while 21 underwent surgery and radiotherapy. Pituitary and hypothalamic deficits were more frequent in treated with surgery, whereas visual defects and metabolic diseases were more frequent in treated with surgery and radiotherapy. There were no differences between age of onset groups and type of sequelae. After diagnosis, nine patients concluded their academic training. In childhood-onset group, after diagnosis, one patient was retired, three continue studying and the others concluded schooling. In the other group, six patients were retired and two concluded schooling. There was no association between academic performance or employability and the type of treatment. CP patients academic performance was not worse comparing with general Portuguese population.

Conclusions: Long-term sequelae may not be related with the age of CP onset, but may vary according to the type of treatment. There was a wide variety of clinical sequelae with extended follow-up, however academic performance and employability seemed not affected. CP diagnosis in an early period of life may not compromise the academic success of patients.