Journal of Endocrinological Investigation最新文献

Purpose: Women with gestational diabetes (GDM) have increased risk of hypertensive disorders in pregnancy (HDP). However, knowledge remains limited for women with high-risk metabolic profiles, regardless of GDM diagnosis. This study aimed to evaluate the prevalence of HDP among women at high risk for GDM, while simultaneously identifying potential predictive clinical risk factors of HDP.

Methods: Pregnant women who performed a 75-gr Oral Glucose Tolerance Test for the selective screening (based on pre-pregnancy risk factors) of GDM were prospectively enrolled (October 2019-June 2022). The development of HDPwas assessed. Logistic regression and ROC-curve analysis were used to identify predictive risk factors for HDP.

Results: Of the 398 women enrolled (53.5% with GDM), 30 (8%) developed HDP. Women developing HDP had more frequently a family history of type 2 diabetes, a personal history of GDM or preeclampsia, and showed higher pregestational BMI and first-trimester fasting plasma glucose. Moreover, at GDM screening, they had higher fasting and 1-hour glucose levels, and higher systolic and diastolic blood pressure. At logistic regression, systolic and diastolic blood pressure were the strongest risk factors for HDP. The risk increased for systolic blood pressure ≥ 127 mmHg (61% sensitivity, 86% specificity, PPV:27%, NPV:86%) and diastolic blood pressure ≥ 82 mmHg (57% sensitivity, 92% specificity, PPV:38%, NPV:96%).

Conclusion: Women at high risk for GDM with poor metabolic profile have higher prevalence of HDP. Systolic and diastolic blood pressure at the time of GDM screening may identify women with higher risk of developing HDP, regardless of GDM diagnosis.

Context: Leukocytosis frequently noted in Cushing's syndrome (CS), along with other blood cell changes caused by direct and indirect cortisol effects.

Objective: Assess baseline white blood cell (WBC) profile in CS patients compared to controls and WBC changes pre- and post-remission after surgical treatment for CS.

Design: A comparative nationwide retrospective cohort study.

Setting: Data from Clalit Health Services database.

Patients: 297 patients (mean age 51 ± 16.1 years, 73.0% women) with CS and 997 age-, sex-, body mass index-, and socioeconomic status-individually matched controls. Ectopic CS or adrenal cancer patients were excluded.

Main outcome measure: Mean WBC, neutrophils, and neutrophil-to-lymphocyte ratio (NLR) two-years before and after pituitary or adrenal surgery. WBC and neutrophils are expressed as Kcells/µl.

Results: At baseline, leukocytosis was observed in 21.5% of patients with CS vs. 8.9% of controls (P < 0.001). Patients with CS had significantly higher WBC (8.8 ± 2.88 vs. 7.54 ± 2.45, p < 0.0001), neutrophils (5.82 ± 2.38 vs. 4.48 ± 1.97, p < 0.0001), and NLR (3.37 ± 2.63 vs. 2.27 ± 1.86, p < 0.0001) compared to controls, regardless of pituitary or adrenal source of hypercortisolemia. Post-surgery, patients with CS experienced significant decreases in mean WBC (-0.57 ± 2.56, p < 0.0001), neutrophils (-0.84 ± 2.55, p < 0.0001), and NLR (-0.63 ± 2.7, p < 0.0001). Despite achieving disease remission, patients with CS still had higher WBC (8.11 ± 2.4 vs. 7.46 ± 2.17, p = 0.0004) and neutrophils (4.71 ± 2.10 vs. 4.41 ± 1.87, p = 0.03) compared to controls. Patients with CD and baseline leukocytosis had lower remission rate than those with normal WBC (36.7% vs. 63.9%, p = 0.01).

Conclusions: At diagnosis, CS patients have elevated WBC, neutrophils, and NLR compared to controls. Remission does not normalize WBC levels in all patients, and baseline leukocytosis predicts a poorer remission prognosis in CD.

Purpose: Elevated methylglyoxal (MGO) levels and altered immune cell responses are observed in diabetes. MGO is thought to modulate immune cell activation. The current study investigated whether fasting or post-glucose-load plasma MGO concentrations are associated with circulating immune cell counts and activation in a large cohort study.

Methods: 696 participants of The Maastricht Study (age 60.3 ± 8.4 years, 51.9% women) underwent an oral glucose tolerance test (OGTT). Fasting and post-OGTT plasma MGO concentrations were measured using mass spectrometry. Numbers and activation of circulating immune cells at fasting state were quantified using flow cytometry. Activation scores were calculated by averaging individual marker z-scores for neutrophils (CD11b, CD11c, CD16) and classical, intermediate, and non-classical monocytes (CD11b, CD11c, CX3XR1, HLA-DR). Associations were analysed using multiple linear regression adjusted for potential confounders. Stratified analyses were performed for glucose metabolism status for associations between plasma MGO levels and immune cell counts.

Results: Higher fasting plasma MGO concentrations were significantly associated with higher numbers of intermediate (β = 0.09 [95%CI 0.02; 0.17]) and non-classical monocytes (0.08 [0.002; 0.15]), but with lower activation scores for the intermediate monocytes (-0.14 [-0.22; -0.06]). Stratified analyses showed that positive associations between fasting plasma MGO levels and numbers of intermediate and non-classical monocytes appear only in participants with type 2 diabetes. Post-OGTT plasma MGO concentrations were not consistently associated with immune cells counts or activation.

Conclusion: Higher fasting plasma MGO concentrations are associated with higher intermediate and non-classical monocyte counts but with lower activation of intermediate monocytes.

Purpose: A paradoxical increase in GH after oral glucose load (GH-Par) characterizes about one-third of acromegaly patients and is associated with a better response to first-generation somatostatin receptor ligands (fg-SRLs). Pasireotide is typically considered as a second-/third-line treatment. Here, we investigated the predictive role of GH-Par in pasireotide response and adverse event development.

Methods: we collected a multicenter Italian retrospective cohort of 59 patients treated with pasireotide for at least 3 months, all having GH profile from OGTT. IGF-1 normalization or at least 30% reduction at the last follow-up visit defined a responder patient.

Results: Considering the entire cohort, median IGF-1 levels before pasireotide (available in 57 patients) were 1.38 times the upper limit of normal (ULN) in patients with large (median size 18 mm) and invasive (82%) adenomas after failure of fg-SRL treatment. After a 40-month median treatment, pasireotide effectively reduced IGF-1 ULN levels in 41 patients, 37 of whom achieving normalization, and 4 with a ≥ 30% reduction. Thirteen patients were classified as GH-Par. The median pasireotide duration, dosage, and efficacy (9/12 responder in the GH-Par group and 32/45 in the GH-NPar) were similar between groups. However, the occurrence of new-onset or worsening glucose metabolism alterations (GMAs) after pasireotide was more frequent in GH-NPar (from 37 to 80%; p < 0.001) compared to GH-Par patients (from 69 to 76%), likely due to the higher prevalence of pre-existing GMAs in the GH-Par group before starting pasireotide (p = 0.038).

Conclusions: The GH-Par does not predict the response to pasireotide in acromegaly but can predict a worse metabolic profile.

Purpose: To gather the current opinion among Italian gynecologists and endocrinologists regarding the definition, diagnosis, and treatment of polycystic ovary syndrome (PCOS).

Method: A Delphi survey consisting of 26 statements was designed by a nine-member panel (consisting of members from the Italian Society of Endocrinology (SIE) and the Experts Group AQon Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS)) and distributed to 102 experts in PCOS across the fields of gynecology and endocrinology. Consensus was defined as an agreement between at least 70% of responders. Participants completed three rounds of statements, ranking their level of agreement.

Results: Of the initial 26 statements, 25 reached an adequate consensus, with an overall response rate of 73%. The statements were divided into three sections: definition and current understanding, diagnosis, and treatment. Of the statements that reached consensus, near total agreement was reached in the first two sections, whereas there was a divergence of opinion in terms of optimum treatment strategy between the gynecology and endocrinology subgroups.

Conclusion: It was agreed that the current clinical guidelines are inadequate for clinical and scientific practice, with most responders advocating for the inclusion of metabolic factors. Furthermore, the consensus opinion advocated for the diversification of hyperandrogenic vs. non-hyperandrogenic phenotypes. This survey gives a snapshot of the current understanding of PCOS in the Italian healthcare community.

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.