Introduction. Wilson’s disease (WD) is a rare genetic disease with autosomal recessive transmission, thus screening of all family members of newly diagnosed patients is recommended. Therefore, we aimed to analyze the proband’s family members to detect asymptomatic cases and early treatment initiation. Material and methods. There were retrospectively evaluated 12 families, between 2008 - 2023. The Leipzig Scoring System was used to assess the diagnosis. Genetic testing was performed in all cases by the Sanger sequencing method, examining exons with a high and moderate frequency of mutations. Results. All patients were of Caucasian origin, and originally from Moldova. No patient reported consanguineous relationships. In 9 families, first-degree relatives were tested - parents and siblings, in the other 3 cases only their descendants were evaluated. In 6/12 cases: both parents were healthy carriers; in the other 3 families, one parent was a healthy carrier, but the other parent had not been tested. Among siblings, 4 healthy carriers and 2 healthy siblings were identified. 7 new family members with WD were identified in 5/12 families. 6 patients were asymptomatic, and 1 - was symptomatic. The most frequent mutations detected were p.H1069Q and p.G1341D, both as compound heterozygous and homozygous recessive. A rare mutation has been detected. Discussions. Genetic counseling is important for the family of the patient with Wilson’s disease, as the evaluation of first-degree relatives is recommended by all international guidelines. First-degree relatives include the proband’s siblings, as well as the proband’s offspring and parents. It is also important to assess distant relatives, especially in more isolated areas. Although it is an autosomal recessive disorder, systemic family screening is recommended, as cases of paradoxical transmission are recorded. The c.2292C>T variant, identified in one patient, represents a rare mutation that, when occurring in combination with another pathogenic mutation or a homozygous state, can cause WD. Conclusions. Family screening greatly influences identifying asymptomatic members with Wilson’s disease. Genetic testing is very important in differentiating healthy carriers from asymptomatic members, especially when deciding treatment tactics.

Background: Irisin, a recently discovered muscle-originating hormone, has been found to act as a biomarker of several ailments, while no guideline clearly indicates its testing so far in any particular population category or pathological condition. Objective: We analyzed blood (circulating) irisin in relation to the potential correlations with the evaluation of glucose and bone profile. Methods: This was a prospective, pilot, exploratory study (between December 2024 and August 2025). The enrolled patients were menopausal women aged ≥50. Exclusion criteria: Endocrine tumors, thyroid dysfunction, malignancies, or chronic kidney disease. Baseline (fasting) testing was followed by 75 g oral glucose tolerance test (OGTT). Enzyme-linked immunosorbent assay (ELISA)-based irisin assay (MyBioSource) was performed. The subjects underwent central Dual-Energy X-Ray Absorptiometry (DXA), which provided lumbar, femoral neck and total hip bone mineral density (BMD)/T-score (GE Lunar Prodigy), and lumbar DXA-based trabecular bone score (TBS iNsight). Results: We enrolled 89 females [mean age of 62.84 ± 9.33 years, average years since menopause (YSM) of 15.94 ± 9.23]. Irisin (102.69 ± 98.14 ng/mL) did not correlate with age, YSM, but with body mass index (r = 0.36, p < 0.001). Bone formation marker osteocalcin (r = −0.25, p = 0.018) was negatively associated with irisin, amidst multiple other mineral metabolism assays (including PTH and 25-hydroxyvitamin D). Irisin positively correlated with insulin (r = 0.385, p = 0.0008), HbA1c (r = 0.243, p = 0.022), and HOMA-IR (r = 0.313, p = 0.007). Additional endocrine assays pointed a statistically significant association between irisin and TSH, respectively, ACTH (r = 0.267, p = 0.01, and r = 0.309, p = 0.041, respectively). No correlation irisin-BMD/T-score/TBS was confirmed. Conclusions: Irisin correlates with markers of glucose status (insulin, HOMA-IR, and HbA1c), as well as body mass index and, to a lesser extent, bone metabolism markers. Interestingly, TSH and ACTH correlations open a new (hypothesis-generating) perspective in the endocrine frame of approaching this exerkine. To the best of our knowledge, no distinct study has so far addressed the TBS–irisin relationship or pinpointed the glucose effects on TBS, particularly in menopausal women.

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways.

Background: Wilson’s disease is a rare, autosomal recessive genetic disorder that affects the biliary excretion of copper and its toxic accumulation in various tissues, especially the liver and brain. It is widespread throughout the world, with a high prevalence in socio-culturally isolated communities. The course of the disease and the age of onset depend on the site of mutation in the gene and the degree of functional impairment of the ATP7B protein. The presence of the compound heterozygous patient complicates the comparative genetic and clinical evaluation. Therefore, it is necessary to analyze Wilson’s variants in both the homozygous and the compound-heterozygous conditions to better understand the genotype-phenotype correlations and the incomplete penetrance observed in this disorder. Outlining clear phenotype-genotype associations is difficult due to a large number of mutations and different clinical presentations, but the involvement of epigenetic factors, modifying genes, environmental and lifestyle factors could explain the differences in evolution and onset in members of the same family and not only. Conclusions: Wilson’s disease is a genetically and clinically complex disorder. Although the results of genotype-phenotype correlation studies are not well defined, and in some cases are completely contradictory, some peculiarities related to the age of onset, sex, clinical phenotype, and the evolution of the disease have been highlighted. The interaction between genetic mutations and epigenetic factors may explain the phenotypic variability, but needs further study.

Background/Objectives: Current musculoskeletal health assessment expanded beyond bone mineral density (BMD) at central DXA to include, for instance, trabecular bone score (TBS) and emergent biomarkers, such as adipokines and myokines (e.g., irisin) assays. A current gap in their application is reflected in limited research regarding adrenal tumors, especially non-functional adrenal tumors/mild autonomous cortisol secretion (NFATs/MACS). To assess this current gap, we aimed to explore beyond BMD, specifically, TBS and circulating irisin, in relation to the adrenal status in NFATs/MACS. Methods: This is a prospective, cross-sectional, single-center, exploratory study, conducted between October 2024 and December 2025. Results: A total of 81 menopausal women were included (mean age of 63.26 ± 8.82 years, 15.86 ± 9.5 years since menopause, average BMI of 30.69 ± 5.76 kg/sqcm. Out of them, 33.33% had NFATs/MCAS (group AI) and 66.67% were controls (group C), with similar age, years since menopause, and BMI. The prevalence of type 2 diabetes was 66.67% versus 68.52% (p = 0.865). TBS correlated with lumbar BMD/T-score (N = 33), while age and lumbar BMD were independent TBS predictors (N = 81), but not type 2 diabetes nor NFAs/MCAS. TBS correlated with the five-year age groups (r = −0.273, p = 0.003). Irisin correlated with osteocalcin (r = −0.252, p = 0.007), P1NP (r = −0.187, p = 0.049) and CrossLaps (r = −0.209, p = 0.026) in tumor-free controls. In the AI group, a higher irisin was associated with a higher second-day cortisol after 1 mg DST (r = 0.11, p = 0.584) and a lower ACTH (r = −0.716, p < 0.001). The rate of low TBS (based on 1.350 cutoffs) was 48.15% versus 38.89% in group AI versus C. In the AI group, patients with low TBS had lower osteocalcin, P1NP, and CrossLaps than those with normal TBS, with a similar rate of type 2 diabetes (which might reduce the bone turnover markers) and MACS-positive prevalence (between 25 and 28%). Conclusions: The median glycated hemoglobin A1c (5.78% versus 5.93%, p = 0.94) and median HOMA-IR (1.53 versus 1.42, p = 0.948) suggest a certain level of glucose control, which might not be reflected in severely damaged bone microarchitecture, as shown by TBS. Irisin may be one of the additional factors in these tumors reflecting the hormonal burden. Irisin was statistically significantly elevated with the increase in BMI groups. To our best awareness, this is the first synchronous analysis of TBS and irisin levels in this type of tumor to address the bone status in relation to the glucose profile and adrenal panel. Noting this is an exploratory, hypothesis-generating study, further research will highlight the true value of TBS and irisin for practitioners in the adrenal field, including multi-layered models of bone status prediction.

Introduction. Wilson's disease represents one of the genetic diseases that has lifelong treatment, which significantly improved the quality of life for patients and reduced the disabling complications associated with the lack of an early diagnosis. Material and methods. A structured search was performed in PubMed and HINARI, using English search terms: "Wilson's disease", "acute liver failure", "cirrhosis", "acute Wilsonian hepatitis", "hepatic manifestation", "chronic liver disease", "asymptomatic Wilson's disease", and "active chronic hepatitis". Results. Wilson's disease can occur at any age and can mimic the presence of other chronic liver diseases. The hepatic expression is highly variable, ranging from asymptomatic presentation to severe liver diseases, such as decompensated cirrhosis and acute liver failure. Any patient with transaminitis and abnormal parameters of cooper metabolism should be comprehensively and carefully evaluated to identify Wilson's disease early and to prevent misdiagnosis or unnecessary therapies. Confirmation of the diagnosis should not exclude the co-existence of other liver diseases. Conclusions. The use of validated and adapted scores for Wilson's disease may facilitate diagnosis, but they cannot be used in acute liver failure. Considering that WD presents itself with great phenotypic diversity and can evolve under the mask of other pathologies, it is necessary to carry out a careful differential diagnosis.