Thyroid Malignancy and Cutaneous Lichen Amyloidosis: Key Points Amid RET Pathogenic Variants in Medullary Thyroid Cancer/Multiple Endocrine Neoplasia Type 2 (MEN2).

We aimed to provide an updated narrative review with respect to the RET pathogenic variants and their implications at the clinical and molecular level in the diagnosis of medullary thyroid cancer (MTC)/multiple endocrine neoplasia (MEN) type 2, particularly with respect to the presence of cutaneous lichen amyloidosis (CLA). We searched English-language, in extenso original articles with no timeline nor study design restriction that were published on PubMed. A traditional interplay stands for CLA and MTC in MEN2 (not MEN3) confirmation. While the connection has been reported for more than three decades, there is still a large gap in understanding and addressing it. The majority of patients with MEN2A-CLA have RET pathogenic variants at codon 634; hence, it suggests an involvement of this specific cysteine residue in both disorders (most data agree that one-third of C634-positive subjects have CLA, but the ranges are between 9% and 50%). Females seem more prone to MEN2-CLA than males. Non-C634 germline RET pathogenic variants included (at a low level of statistical evidence) the following: RET V804M mutation in exon 14 for MTC-CLA (CLA at upper back); RET S891A mutation in exon 15 binding OSMR variant G513D (familial MTC and CLA comprising the lower legs to thighs, upper back, shoulders, arms, and forearms); and C611Y (CLA at interscapular region), respectively. Typically, CLA is detected at an early age (from childhood until young adulthood) before the actual MTC identification unless RET screening protocols are already applied. The time frame between CLA diagnosis and the identification of RET pathogenic variants was between 5 and 60 years according to one study. The same RET mutation in one family is not necessarily associated with the same CLA presentation. In MTC/MEN2 subjects, the most affected CLA area was the scapular region of the upper back. Alternatively, another hypothesis highlighted the fact that CLA is secondary to long-term prurit/notalgia paresthetica (NP) in MTC/MEN2. OSMR p. G513D may play a role in modifying the evolutionary processes of CLA in subjects co-harboring RET mutations (further studies are necessary to sustain this aspect). Awareness in CLA-positive patients is essential, including the decision of RET testing in selected cases.

Redo Thyroidectomy: Updated Insights.

The risk of post-operatory hypothyroidism and hypocalcaemia, along with recurrent laryngeal nerve injury, is lower following a less-than-total thyroidectomy; however, a previously unsuspected carcinoma or a disease progression might be detected after initial surgery, hence indicating re-intervention as mandatory (so-called "redo" surgery) with completion. This decision takes into consideration a multidisciplinary approach, but the surgical technique and the actual approach is entirely based on the skills and availability of the surgical team according to the standard protocols regarding a personalised decision. We aimed to introduce a review of the most recently published data, with respect to redo thyroid surgery. For the basis of the discussion, a novel vignette on point was introduced. This was a narrative review. We searched English-language papers according to the key search terms in different combinations such as "redo" and "thyroid", alternatively "thyroidectomy" and "thyroid surgery", across the PubMed database. Inclusion criteria were original articles. The timeframe of publication was between 1 January 2020 and 20 July 2024. Exclusion criteria were non-English papers, reviews, non-human studies, case reports or case series, exclusive data on parathyroid surgery, and cell line experiments. We identified ten studies across the five-year most recent window of PubMed searches that showed a heterogeneous spectrum of complications and applications of different surgeries with respect to redo interventions during thyroid removal (e.g., recurrent laryngeal nerve monitoring during surgery, other types of incision than cervicotomy, the use of parathyroid fluorescence, bleeding risk, etc.). Most studies addressing novel surgical perspectives focused on robotic-assisted re-intervention, and an expansion of this kind of studies is expected. Further studies and multifactorial models of assessment and risk prediction are necessary to decide, assess, and recommend redo interventions and the most adequate surgical techniques.

The Constellation of Risk Factors and Paraneoplastic Syndromes in Cholangiocarcinoma: Integrating the Endocrine Panel Amid Tumour-Related Biology (A Narrative Review).

Cholangiocarcinomas (CCAs), a heterogeneous group of challenging malignant tumours which originate from the biliary epithelium, are associated with an alarming increasing incidence during recent decades that varies between different regions of the globe. Thus, awareness represents the key operating factor. Our purpose was to overview the field of CCAs following a double perspective: the constellation of the risk factors, and the presence of the paraneoplastic syndromes, emphasizing the endocrine features amid the entire multidisciplinary panel. This is a narrative review. A PubMed-based search of English-language original articles offered the basis of this comprehensive approach. Multiple risk factors underlying different levels of statistical evidence have been listed such as chronic biliary diseases and liver conditions, inflammatory bowel disease, parasitic infections (e.g., Opisthorchis viverrini, Clonorchis sinensis), lifestyle influence (e.g., alcohol, smoking), environmental exposure (e.g., thorotrast, asbestos), and certain genetic and epigenetic interplays. With regard to the endocrine panel, a heterogeneous spectrum should be taken into consideration: non-alcoholic fatty liver disease, obesity, type 2 diabetes mellitus, and potential connections with vitamin D status, glucagon-like peptide 1 receptor, or the galanin system, respectively, with exposure to sex hormone therapy. Amid the numerous dermatologic, hematologic, renal, and neurologic paraneoplastic manifestations in CCAs, the endocrine panel is less described. Humoral hypercalcaemia of malignancy stands as the most frequent humoral paraneoplastic syndrome in CCAs, despite being exceptional when compared to other paraneoplastic (non-endocrine) manifestations and to its reported frequency in other (non-CCAs) cancers (it accompanies 20-30% of all cancers). It represents a poor prognosis marker in CCA; it may be episodic once the tumour relapses. In addition to the therapy that targets the originating malignancy, hypercalcaemia requires the administration of bisphosphonates (e.g., intravenous zoledronic acid) or denosumab. Early detection firstly helps the general wellbeing of a patient due to a prompt medical control of high serum calcium and it also provides a fine biomarker of disease status in selected cases that harbour the capacity of PTHrP secretion. The exact molecular biology and genetic configuration of CCAs that display such endocrine traits is still an open matter, but humoral hypercalcaemia adds to the overall disease burden.

Superficial Vein Thrombosis in an Asymptomatic Case of Cholangiocarcinoma with Recent History of COVID-19.

The COVID-19 pandemic brought into prominence several emergent medical and surgical entities, but, also, it served as trigger and contributor for numerous apparently unrelated ailments such as arterial and venous thromboembolic complications. Additional risk factors for these thrombotic traits may be concurrent (known or unknown) malignancies, including at hepatic level. Among these, cholangiocarcinoma (CCA), a rare cancer of intra- and extra-hepatic biliary ducts, represents a very aggressive condition that typically associates local and distant advanced stages on first presentation requiring a prompt diagnosis and a stratified management. This neoplasia has been reported to present a large spectrum of paraneoplastic syndromes in terms of dermatologic, renal, systemic, neurologic, endocrine, and cardiovascular settings, that, overall, are exceptional in their epidemiologic impact when compared to other cancers. Our aim was to introduce a most unusual case of CCA-associated distant thrombosis in a male adult who initially was considered to experience COVID-19-related thrombotic features while having a history of obesity and bariatric surgery. This is a hybrid type of paper: this clinical vignette is accompanied by two distinct sample-focused analyses as a basis for discussion; they each had different methods depending on their current level of statistical evidence. We only included English-published articles in PubMed, as follows: Firstly, we conducted a search of reports similar to the present case, regarding distant vein thrombosis in CCA, from inception until the present time. We performed a literature search using the keywords "cholangiocarcinoma", "thrombosis", and "Trousseau's syndrome" and identified 20 cases across 19 original papers; hence, the current level of evidence remains very low Secondly, we searched for the highest level of statistical evidence concerning the diagnosis of venous thrombosis/thromboembolism in patients who underwent COVID-19 infection (key search terms were "COVID-19", alternatively, "coronavirus", and "SARS-CoV-2", and "thrombosis", alternatively, "thromboembolism") and included the most recent systematic reviews and meta-analyses that were published in 2024 (from 1 January 2024 until 8 July 2024). After excluding data on vaccination against coronavirus or long COVID-19 syndrome, we identified six such articles. To conclude, we presented a probably unique case of malignancy with an initial manifestation consisting of recurrent superficial vein thrombosis under anticoagulation therapy, with no gastrointestinal manifestations, in a patient with a notable history for multiple episodes of SARS-CoV-2 infection and a prior endocrine (gastric) surgery. To our knowledge, this is the first identification of a CCA under these specific circumstances.

Diabetes Mellitus in Non-Functioning Adrenal Incidentalomas: Analysis of the Mild Autonomous Cortisol Secretion (MACS) Impact on Glucose Profile.

Non-functioning adrenal incidentalomas (NFAIs) have been placed in relationship with a higher risk of glucose profile anomalies, while the full-blown typical picture of Cushing's syndrome (CS) and associated secondary (glucocorticoid-induced) diabetes mellitus is not explicitly confirmed in this instance. Our objective was to highlight the most recent data concerning the glucose profile, particularly, type 2 diabetes mellitus (T2DM) in NFAIs with/without mild autonomous cortisol secretion (MACS). This was a comprehensive review of the literature; the search was conducted according to various combinations of key terms. We included English-published, original studies across a 5-year window of publication time (from January 2020 until 1 April 2024) on PubMed. We excluded case reports, reviews, studies on T1DM or secondary diabetes, and experimental data. We identified 37 studies of various designs (14 retrospective studies as well 13 cross-sectional, 4 cohorts, 3 prospective, and 2 case-control studies) that analysed 17,391 individuals, with a female-to-male ratio of 1.47 (aged between 14 and 96 years). T2DM prevalence in MACS (affecting 10 to 30% of NFAIs) ranged from 12% to 44%. The highest T2DM prevalence in NFAI was 45.2% in one study. MACS versus (non-MACS) NFAIs (n = 16) showed an increased risk of T2DM and even of prediabetes or higher fasting plasma glucose or HbA1c (no unanimous results). T2DM prevalence was analysed in NFAI (N = 1243, female-to-male ratio of 1.11, mean age of 60.42) versus (non-tumour) controls (N = 1548, female-to-male ratio of 0.91, average age of 60.22) amid four studies, and two of them were confirmatory with respect to a higher rate in NFAIs. Four studies included a sub-group of CS compared to NFAI/MACS, and two of them did not confirm an increased rate of glucose profile anomalies in CS versus NFAIs/ACS. The longest period of follow-up with concern to the glycaemic profile was 10.5 years, and one cohort showed a significant increase in the T2DM rate at 17.9% compared to the baseline value of 0.03%. Additionally, inconsistent data from six studies enrolling 1039 individuals that underwent adrenalectomy (N = 674) and conservative management (N = 365) pinpointed the impact of the surgery in NFAIs. The regulation of the glucose metabolism after adrenalectomy versus baseline versus conservative management (n = 3) was improved. To our knowledge, this comprehensive review included one of the largest recent analyses in the field of glucose profile amid the confirmation of MACS/NFAI. In light of the rising incidence of NFAI/AIs due to easier access to imagery scans and endocrine evaluation across the spectrum of modern medicine, it is critical to assess if these patients have an increased frequency of cardio-metabolic disorders that worsen their overall comorbidity and mortality profile, including via the confirmation of T2DM.

Psychological Factors Associated with General Quality of Life in the Context of COVID-19 Pandemic: A Cross-Sectional Study on a Multicultural Sample of Romanian Medical Students.

The COVID-19 pandemic had a significant impact on the general quality of life (GQOL) of a large number of individuals, including those in the academic environment. This study investigated GQOL in a sample of 613 Romanian medicine students (81.57% were female; mean age = 21.40 ± 1.749 years) in relation to their Big Five personality characteristics, Perceived Stress and Fear of COVID-19. The study was conducted between June 2020 and March 2022. These variables were investigated with the Big Five Inventory-2: Extra-Short Form, the Fear of COVID-19 Scale (FCV-19S), the Perceived Stress Scale-10 and the Satisfaction with Life Scale (SWLS). Statistical analysis included hierarchical linear regression and t-tests. The results indicated a significant direct relationship between GQOL and the personality traits of Conscientiousness, Extraversion and Agreeableness. However, a significant inverse relationship was observed between GQOL and Perceived Stress and Neuroticism. Fear of COVID-19 was significantly higher in women, while no other socio-demographic variables were associated with GQOL. A total of 61.7% of the studied population returned to their original residency during the pandemic years. These results could be important for better understanding the vulnerability to significant epidemiological events in academic populations and for planning adequate preventive or interventional measures.

Leptin Is Associated with Testosterone, Nutritional Markers, and Vascular Muscular Dysfunction in Chronic Kidney Disease.

Chronic kidney disease (CKD) causes specific hormonal disturbances, such as variations in leptin and testosterone levels and function. These disturbances can promote errors in signaling interaction and cellular information processing and can be implicated in the pathogenesis of atherosclerosis. This study investigates the factors that affect leptin in CKD patients and examines how leptin is related to markers of vascular disease. We conducted a cross-sectional study of 162 patients with CKD in pre-dialysis and dialysis stages. We recorded clinical and laboratory data, including leptin, testosterone, and subclinical atherosclerosis markers like brachial-ankle pulse wave velocity (ba PWV) in pre-dialysis CKD patients and flow-mediated vasodilation (FMD) and nitroglycerin-mediated vasodilation (NMD) in hemodialysis (HD) patients. Leptin was significantly correlated with testosterone in CKD pre-dialysis stages (p < 0.001) and also in HD (p = 0.026), with adipose tissue mass in pre-dialysis stages (p < 0.001), and also in HD (p < 0.001). In women HD patients, leptin correlated with NMD (p = 0.039; r = -0.379); in all HD patients, leptin correlated with C reactive protein (p = 0.007; r = 0.28) and parathormone (p = 0.039; r = -0.220). Our research emphasizes the connection between leptin, adipose tissue, and testosterone in all stages of CKD. Leptin was associated with NMD in HD women and correlated with inflammatory syndrome and parathyroid hormone in all HD patients.

Brown Tumors: The Hidden Face of Primary and Renal Hyperparathyroidism Amid Real-Life Settings.

Brown tumors, an exceptional bone complication of severe primary (PHP) or renal (secondary) hyperparathyroidism (RHP), are caused by long-standing, elevated parathormone (PTH)-induced osteoclast activation causing multinucleated giant cell conglomerates with hemosiderin deposits in addition to the local production of cytokines and growth factors. We aim to present an adult case series including two females displaying this complication as part of a multidisciplinary complex panel in high PTH-related ailments. The approach was different since they had distinct medical backgrounds and posed a wide area of challenges amid real-life settings, namely, a 38-year-old lady with PHP and long-term uncontrolled hypercalcemia (with a history of pregnancy-associated PHP, the removal of a cystic jaw tumor, as well as a family and personal positive diagnosis of polycystic kidney disease, probably a PHP-jaw tumor syndrome), as well as, a 26-year-old woman with congenital single kidney and chronic renal disease-associated RHP who was poorly controlled under dialysis and developed severe anemia and episodes of metabolic acidosis (including one presentation that required emergency hemodialysis and was complicated with convulsive seizures, followed by resuscitated respiratory arrest). Both subjects displayed a severe picture of PHP/RHP with PTH levels of >1000 pg/mL and >2000 pg/mL and elevated serum bone turnover markers. Additionally, they had multiple brown tumors at the level of the ribs and pelvis (asymptomatically) and the spine, skull, and pelvis (complicated with a spontaneous cervical fracture). As an endocrine approach, the control of the underlying parathyroid disease was provided via surgery in PHP (for the postparathyroidectomy hungry bone syndrome) via medical intervention (with vitamin D analogs) in RHP. Additionally, in this case, since the diagnosis was not clear, a multidisciplinary decision to perform a biopsy was taken (which proved inconclusive), and the resection of the skull tumor to confirm the histological traits. This series highlights the importance of addressing the entire multidisciplinary panel of co-morbidities for a better outcome in patients with PHP/RHP-related brown tumors. However, in the instance of real-life medicine, poor compliance and reduced adherence to recommendations might impair the overall health status. Thus, sometimes, a direct approach at the level of cystic lesion is taken into consideration; this stands for a narrow frame of decision, and it is a matter of personalized decision. As seen here, brown tumors represent the hidden face of PHP/RHP, primarily the complex and severe forms, and awareness is essential even in the modern era.

Inquiry of the Metabolic Traits in Relationship with Daily Magnesium Intake: Focus on Type 2 Diabetic Population.

Magnesium (Mg), an essential nutrient with a wide area of physiological roles, stands as a cofactor in over 600 enzymatic reactions involved in the synthesis of proteins and nucleic acids, DNA repair, neuromuscular functions, neuronal transmission, cardiac rhythm regulation, and the modulation of metabolic pathways, as well as acting as a natural blocker for the calcium channels. Our objective was to highlight the most recent clinical data with respect to daily Mg intake (DMI) and metabolic traits, particularly type 2 diabetes mellitus (DM). This was a PubMed-based review of the English-language medical papers across different key terms of search; the time frame was from January 2019 until April 2024. We included (clinically relevant) original studies and excluded cases reports, series, reviews, editorials, opinion, experimental studies, and non-human data as well as studies that did not specifically assessed DMI and only provided assays of serum Mg, studies on patients diagnosed with type 1 or secondary DM. A total of 30 studies were included and we organized the key findings into several sections as follows. Studies investigating DMI in relationship with the adherence to local recommendations in diabetic subjects (n = 2, one transversal and another retrospective cohort; N = 2823) found that most of them had lower DMI. Deficient DMI was correlated with the risk of developing/having DM across five studies (n = 5, one prospective and four of cross-sectional design; N = 47,166). An inverse correlation between DMI and DM prevalence was identified, but these data are presented amid a rather heterogeneous spectrum. Four novel studies (N = 7279) analysed the relationship between DMI and DM control according to various methods (HbA1c, fasting and postprandial glycaemia, and insulin); the association may be linear in diabetic subjects only at certain levels of DMI; additionally, the multifactorial influence on HBA1c should take into consideration this dietary determinant, as well, but there are no homogenous results. Three studies concerning DMI and diabetic complications (one cross-sectional, one prospective, and another case-control study) in terms of retinopathy (n = 1, N = 3794) and nephropathy (n = 2, N = 4805) suggested a lower DMI was associated with a higher risk of such complications. Additionally, two other studies (one prospective and one retrospective cohort) focused on mortality (N = 6744), which, taking only certain mortality indicators into consideration, might be decreased in the subgroups with a higher DMI. Seven studies (N = 30,610) analysed the perspective of DMI in the general population with the endpoint of different features amid glucose profile, particularly, insulin resistance. Concerning HOMA-IR, there were three confirmatory studies and one non-confirmatory, while fasting plasma glucose was highlighted as inversely correlated with a DMI (n = 1). The highest level of evidence regarding Mg supplementation effects on glucose metabolism stands on seven randomised controlled trials (N = 350). However, the sample size was reduced (from 14 to 86 individuals per study, either diabetic or pre-diabetic) and outcomes were rather discordant. These clinical aspects are essential from a multidisciplinary perspective and further trials are mandatory to address the current areas of discordant results.

Endocrine Petrified Ear: Associated Endocrine Conditions in Auricular Calcification/Ossification (A Sample-Focused Analysis).

Petrified ear (PE), an exceptional entity, stands for the calcification ± ossification of auricular cartilage (CAC/OAC); its pathogenic traits are still an open matter. Endocrine panel represents one of the most important; yet, no standard protocol of assessments is available. Our objective was to highlight most recent PE data and associated endocrine (versus non-endocrine) ailments in terms of presentation, imagery tools, hormonal assessments, biopsy, outcome, pathogenic features. This was a comprehensive review via PubMed search (January 2000-March 2024). A total of 75 PE subjects included: 46 case reports/series (N = 49) and two imagery-based retrospective studies (N = 26) with CAC/OAC prevalence of 7-23% (N = 251) amid routine head/temporal bone CT scans. Endocrine PE (EPE): N = 23, male/female ratio = 10.5; average age = 56.78, ranges: 22-79; non-EPE cohort: N = 26; male/female ratio = 1.88, mean age = 49.44; ranges: 18-75 (+a single pediatric case).The longest post-diagnosis follow-up was of 6-7 years. The diagnosis of PE and endocrine anomalies was synchronous or not (time gap of 10-20 years). A novel case in point (calcified EPE amid autoimmune poly-endocrine syndrome type 2 with a 10-year post-diagnosis documented follow-up) was introduced. We re-analyzed EPE and re-classified another five subjects as such. Hence, the final EPE cohort (N = 50) showed: adrenal insufficiency was the most frequent endocrine condition (36%) followed by hypopituitarism (22%) and hypothyroidism (18%); 39% of the patients with adrenal failure had Addison's disease; primary type represented 72% of all cases with hypothyroidism; an endocrine autoimmune (any type) component was diagnosed in 18%. We propose the term of "endocrine petrified ear" and a workflow algorithm to assess the potential hormonal/metabolic background in PE.