Journal of Endocrinological Investigation最新文献

Purpose: The delayed or missed diagnosis of secondary hypertension contributes to the poor blood pressure control worldwide. This study aimed to assess the diagnostic approach to primary aldosteronism (PA) and pheochromocytoma (PHEO) among Italian centers associated to European and Italian Societies of Hypertension.

Methods: Between July and December 2023, a 10-items questionnaire was administered to experts from 82 centers of 14 Italian regions and to cardiologists from the ARCA (Associazioni Regionali Cardiologi Ambulatoriali) Piemonte. Results were stratified for geographical area, specialty, and center category (excellence vs. non-excellence centers).

Results: Each center diagnosed an average of 2 cases of PA and 0.2 cases of PHEO annually, with higher figures in excellence centers. PA screening is performed mainly in patients with resistant hypertension (73.2%) or hypertension and spontaneous hypokalemia (84.1%), while only 17.1% and 35.4% of centers screen patients with grade 2-3 hypertension. Screening rate is lower for cardiologists compared to other specialists. The main barriers to wider testing were challenges in interpreting the aldosterone/renin ratio under interfering medications and switching to non-interfering drugs. Clinical scores to predict the likelihood of PA and the definition of Standard Operating Procedures were identified as potential tools to boost screening rates. Testing for PHEO was mostly conducted in patients with typical symptoms (75.6%) and/or hypertensive crisis (74.4%). Only 37.8% of centers screened all patients with adrenal incidentaloma.

Conclusion: This study highlights significant gaps in the screening and diagnosis of PA and PHEO across Italian centers and underscores the need for widespread and standardized diagnostic protocols.

Purpose: Type 2 deiodinase (D2), encoded by DIO2 gene, catalyzes the activation of the prohormone thyroxine (T4) into the bioactive hormone triiodothyronine (T3) in peripheral tissues, thereby regulating the intracellular Thyroid Hormone (TH) availability. Recently, several studies have demonstrated that a drastic increase in the peripheral activation of TH, via D2, fosters tumor progression, metastasis, and immunity.

Methods: To further prove the clinical relevance of D2 in human cancer, based on public Database of The Cancer Genome Atlas (TCGA), we conducted a pan-cancer analysis of DIO2 expression in various cancer types and investigated the association of DIO2 expression with the tumor microenvironment (TME) components and immune cell infiltration, along with the DIO2 genetic alteration types.

Results: Although with different expression levels between the various cancer types, the pan-cancer analysis showed that DIO2 was highly expressed in most tumors and related to the progression of some tumor types. Furthermore, DIO2 expression was also significantly correlated with TME components, immune cell infiltration, and immunoinhibitory and immunostimulatory gene subsets.

Conclusion: The relevance of this study is that it adds a clinical relevance to the recent demonstrations that D2 accelerates tumor invasion in animal models and poses DIO2 gene as a potential prognostic marker in various human cancers.

Purpose: Galactosemia is a rare inborn error of galactose metabolism. There are several forms, the most severe being classic galactosemia (CG), which begins in the first few days of life. Nowadays, it is possible to screen CG at birth, averting acute decompensation or death through diet. Although early dietary interventions help manage acute symptoms, long-term complications still occur, particularly primary ovarian insufficiency (POI) in female patients. This systematic review aims to synthesize existing literature on the relationship between galactosemia and POI, exploring the underlying mechanisms of pathophysiology, hormonal balance, metabolic control, fertility, and management.

Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses and PROSPERO. We queried the SCOPUS and PubMed databases using individual keywords and MeSH terms.

Results: Despite various proposed mechanisms, such as FSH dysfunction and the accumulation of galactose-1-phosphate, the exact cause of POI remains unclear, with studies showing variable correlations between genotype, galactose levels, and ovarian function. Monitoring AMH in prepubertal galactosemia patients may predict POI. Early estrogen replacement therapy, calcium supplementation, and strategies to improve galactosylation should be considered to enhance bone mineralization, given the impact of hypogonadism and low calcium intake on bone density in these patients. The course of POI in women with CG is unpredictable, with recent studies showing that nearly 30% of those attempting to conceive succeeded within a year, a rate that increases to almost 50% after two years.

Conclusion: Despite advancements in understanding and managing CG, POI remains a significant clinical challenge, necessitating ongoing research and a multidisciplinary approach to enhance the long-term health of affected individuals.

Purpose: Infertility is defined as the inability to conceive after 1 year of unprotected intercourse, affecting approximately 15-20% of couples in Western countries. It is a shared problem within the couple; when the main issue lies with one of the partners, it is preferable to refer to "male factor" or "female factor" infertility rather than simply male or female infertility. Despite male factor infertility accounting for half of all couple infertility cases, the clinical approach to the male partner is not uniformly standardized across international guidelines.

Methods: To provide an expert overview, we have comprehensively reviewed and critically analyzed the most up-to-date literature on this sensitive topic, leading to the development of a proposal for tailored assessment of the diagnostic-therapeutic pathway and preventive strategies. The diagnostic approach also considers that infertile men are objectively less healthy than their fertile counterparts of the same age and ethnicity.

Results: This article discusses the diagnostic flow, the classification of male factor infertility, the definition of idiopathic infertility, the involvement of general health, and treatment recommendations, emphasizing follicle-stimulating hormone treatment in selected groups of patients.

Conclusion: We provide expert opinion on current drawbacks and future perspectives in this field, with practical advice for the clinical practice of general practitioners and expert in reproductive medicine.

Purpose: Long noncoding RNAs (lncRNAs) play crucial regulatory roles in the tumorigenesis and progression of various cancers. However, the functional roles of lncRNAs in papillary thyroid cancer (PTC) remain unclear. In this study, we investigated the functional role of the lncRNA FAM111A-DT in PTC progression and the underlying mechanisms.

Methods: Different expression levels of lncRNAs in PTC were compared via analysis of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Bioinformatics analyses and qRT‒PCR were used to investigate the expression of FAM111A-DT in PTC. Cell proliferation was measured via CCK8, EdU, colony formation, and flow cytometry assays. Cell migration and invasion were examined by wound healing and Transwell assays. Apoptosis was detected via flow cytometry. RNA sequencing, qRT‒PCR, Western blot, immunofluorescence and dual-luciferase reporter assays were performed to assess the underlying mechanisms involved.

Results: FAM111A-DT was highly expressed in PTC and associated with poor prognosis, thyroid dedifferentiation, various clinical features and the BRAF^V600E mutation in PTC patients. Overexpression of FAM111A-DT enhanced the proliferation, migration and invasion of PTC cells while reducing their degree of apoptosis. The NF-κB signaling pathway was activated in FAM111A-DT-overexpressing PTC cells. The NF-κB inhibitor PDTC attenuated the promotive effects of FAM111A-DT on aggressive phenotypes and NF-κB pathway activity in PTC cells.

Conclusion: FAM111A-DT is upregulated in PTC, and its expression is associated with poor clinical outcomes. FAM111A-DT plays an oncogenic role by, at least partially, activating the NF-κB signaling pathway.

Background: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus and has the complex pathogenesis. The previous study reported that protein kinase Bγ (AKT3) was involved in DN progression. Our aim was to explore the detailed mechanisms of AKT3 in DN development.

Methods: RT-qPCR was performed to measure the levels of specificity protein 1 (SP1) and AKT3. Mesangial cells were treated with high glucose (30 mM) to form DN cell model in vitro. Western blot was conducted to detect the protein expression of AKT3, SP1, fibrosis-related proteins, and AKT/mTOR pathway-related proteins. Cell proliferation and inflammation were evaluated via MTT, EdU staining, and ELISA assays, respectively. Oxidative stress was determined via measuring ROS and MDA levels. ChIP and dual-luciferase reporter assays were carried out to verify the relationship between SP1 and AKT3. C57BL/6 mice-treated with streptozotocin for 5 days were used to establish DN mouse model in vivo, and HE and Masson staining were conducted to evaluate pathological changes of mouse kidney tissues.

Results: AKT3 and SP1 were highly expressed in DN kidney tissues and HG-induced mesangial cells. AKT3 depletion could relieve HG treatment-caused cell damage of mesangial cells through repressing cell proliferation, fibrosis, inflammation and oxidative stress. SP1 can bind to the promoter of AKT3 and serve as a translation regulation factor of AKT3. SP1 overexpression worsened HG treatment-caused cell damage of mesangial cells. Moreover, AKT3 upregulation could block the suppressive effects of SP1 depletion on cell proliferation, fibrosis, inflammation and oxidative stress in HG-induced mesangial cells. SP1 depletion reduced AKT3 expression to inactivate the AKT/mTOR pathway in HG-induced mesangial cells. Besides, AKT3 knockdown inhibited the activation of the AKT/mTOR pathway to hamper the development of DN in mice through alleviating fibrosis and inflammation in vivo.

Conclusion: Our results indicated that SP1 activated AKT3 and AKT/mTOR pathway to promote mesangial cell proliferation, fibrosis, inflammation and oxidative stress, thereby facilitating DN development.

Representation of exophthalmos in ancient artworks is reported by several authors. In the present paper we analyze a sculpture belonging to the V century AD, likely embodying the eastern Roman emperor Leo I. As the portrait statue is sculpted with uncommon prominent eyes, we discuss the possibility that the historical personage was affected by exophthalmos due to Graves' orbitopathy.

Aim: This review aims to overview factors contributing to TAO development and addresses the targeted diagnostic work-up and treatment management in adult thalassemic patients.

Results: Osteoporosis management in Thalassemia is challenging because several factors contributing to its pathogenesis should be considered and controlled starting from child- hood. A multidisciplinary approach is crucial. Evidence concerning the efficacy of available anti-osteoporosis drugs in thalassemic patients is scarce. In this scenario, clinical experience and center resources often guide the treatment choice. More efforts should be made to share knowledge in this field in order to indicate specific treatment strategies for TAO management.

Methods: We performed a literature search in Pubmed from 1992 to March 2024 using the words Thalassemia and: osteoporosis, Bisphosphonates, Denosumab, Teriparatide, Romosozumab, hormone replacement therapy, growth hormone, hypogonadism, calcium, vitamin D, bone disease, sarcopenia. The search was limited to English literature including original studies, reviews, meta-analyses, case reports.

Purpose: Previous studies show that transgender and gender-diverse (TGD) individuals, especially those assigned male at birth (AMAB), often have low bone mineral density (BMD) before beginning gender-affirming hormone therapy (GAHT). The reasons for this are not fully understood, and the potential role of androgen receptor (AR) polymorphisms - known to affect bone density in the general population - has not been explored. This study aims to assess the impact of AR polymorphisms on bone health in the TGD population.

Methods: This is an observational study involving 135 TGD and 107 cisgender participants. Collected data included hormonal profiles and phospho-calcium metabolism, bone geometry and density (Dual Energy X-ray Absorptiometry and peripheral Quantitative Computed Tomography). For the genetic study related to the AR, genomic DNA was extracted from peripheral blood leukocytes.

Results: TGD individuals had lower BMD values compared to their cisgender peers. In a subgroup of 129 individuals (86 TGD and 43 cisgender), we assessed the length of the polymorphic tracts of the AR gene and observed no differences between the groups. AR polymorphisms showed significant correlations only with cortical BMD in both TGD and cisgender assigned females at birth (AFAB) individuals, and negative correlations with trabecular BMD in both cisgender men and women.

Conclusions: Our study suggests that AR polymorphisms do not play a significant role in the low BMD values observed in TGD individuals at baseline. Further research is necessary to better understand the impact of factors such as lifestyle on the bone health of TGD individuals.

Purpose: The use of thyroid hormones (TH) to treat obesity is unsupported by evidence as reflected in international guidelines. We explored views about this practice, and associations with respondent characteristics among European thyroid specialists.

Methods: Specialists from 28 countries were invited to a survey via professional organisations. The relevant question was whether "Thyroid hormones may be indicated in biochemically euthyroid patients with obesity resistant to lifestyle interventions".

Results: Of 17,232 invitations 5695 responses were received (33% valid response rate; 65% women; 90% endocrinologists). Of these, 290 (5.1%) stated that TH may be indicated as treatment for obesity in euthyroid patients. This view was commoner among non-endocrinologists (8.7% vs. 4.7%, p < 0.01), private practice (6.5% vs. 4.5%, p < 0.01), and varied geographically (Eastern Europe, 7.3%; Southern Europe, 4.8%; Western Europe, 2.7%; and Northern Europe, 2.5%). Respondents from Northern and Western Europe were less likely to use TH than those from Eastern Europe (p < 0.01). Gross national income (GNI) correlated inversely with this view (OR 0.97, CI: 0.96-0.97; p < 0.001). Having national guidelines on hypothyroidism correlated negatively with treating obesity with TH (OR 0.71, CI: 0.55-0.91).

Conclusions: Despite the lack of evidence, and contrary to guidelines' recommendations, about 5% of respondents stated that TH may be indicated as a treatment for obesity in euthyroid patients resistant to life-style interventions. This opinion was associated with (i) respondent characteristics: being non-endocrinologist, working in private practice, treating a small number of hypothyroid patients annually and (ii) national characteristics: prevalence of obesity, Eastern Europe, low GNI and lack of national hypothyroidism guidelines.