Acromegaly is commonly associated with cardiomyopathy due to chronic overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), leading to biventricular hypertrophy, diastolic dysfunction, and in advanced cases, systolic dysfunction and heart failure. This case report presents a 42-year-old male diagnosed with acromegaly, who underwent successful resection of a pituitary macroadenoma. At diagnosis, GH was 12.0 [ng/mL] and IGF-1 was 670 [ng/mL] (age-adjusted ULN: 218). An oral glucose tolerance test was performed; GH failed to suppress below 7.20 [ng/mL]. Despite surgical intervention, the patient experienced persistent cardiac symptoms including exertional dyspnea and breathlessness, which prompted further cardiovascular evaluation. Cardiac examinations revealed significant hypertrophy of the interventricular septum and the left ventricular anterior wall, findings confirmed by echocardiography and cardiac magnetic resonance. Remarkably, genetic analysis identified a heterozygous mutation in the MYBPC3 gene, known to cause hypertrophic cardiomyopathy. This mutation likely exacerbated the patient's cardiac condition, suggesting a compounded effect of acromegaly and a genetic predisposition to cardiomyopathy. This case underscores the importance of considering genetic factors in acromegalic patients presenting with cardiomyopathy to tailor personalized management strategies. Further research is warranted to explore the interplay between hormonal excess and genetic mutations in cardiomyopathy development.
Idiopathic infantile hypercalcemia (IIH) is a rare, parathyroid hormone (PTH)-independent disorder of calcium metabolism. It is most often caused by mutations in the CYP24A1 gene that impair vitamin D catabolism. We report a 70-year-old male with persistent hypercalcemia (Ca 13.2 mg/dL) and low-normal PTH levels. Extensive evaluation excluded malignancy, granulomatous disease, and vitamin D intoxication. Genetic analysis revealed a homozygous CYP24A1 variant (c.233G>T; p.Gly78Val), consistent with CYP24A1 deficiency. Bisphosphonate therapy with zoledronic acid rapidly and sustainably normalized calcium levels for 10 months. The patient's daughter was a heterozygous carrier. This confirmed autosomal-recessive inheritance. This case illustrates an atypical late-onset presentation of CYP24A1 deficiency. It emphasizes the importance of considering this diagnosis in adults with PTH-independent hypercalcemia, especially when seasonal variation and family history are present. Recognition of CYP24A1 deficiency at all ages highlights the need for genotype-based terminology rather than the misleading label "infantile" hypercalcemia.
Context:Accurate diagnosis of adrenal insufficiency (AI) is crucial to prevent potentially life-threatening complications. Early-morning basal serum cortisol is widely used to guide further testing, its diagnostic performance varies across clinical settings. Objective:To evaluate the diagnostic performance of early-morning basal cortisol in patients referred for ACTH stimulation testing and to determine whether basal cortisol alone can reliably exclude AI. Design and Methods:This retrospective cohort study included 404 adult outpatients (mean age 45.3 years; 18.8% male) who underwent standard-dose ACTH (250 µg) stimulation testing between 2018 and 2022. All consecutive patients with available early-morning basal cortisol measurements were included. AI was defined as a peak cortisol response <18 µg/dL (≈497 nmol/L). Diagnostic performance was assessed using logistic regression and receiver operating characteristic (ROC) analyses. Results:AI was diagnosed in 27 patients (6.7%). Basal cortisol levels were inversely associated with ACTH test failure and demonstrated moderate discriminatory ability (AUC = 0.85). Despite higher basal cortisol being associated with lower AI probability, a small proportion of patients within clinically relevant cortisol ranges still failed stimulation testing. Conclusion:Early-morning basal cortisol provides valuable diagnostic information but cannot reliably exclude adrenal insufficiency when used alone. Confirmatory dynamic testing remains necessary to ensure diagnostic safety.
Context:Postoperative hypoparathyroidism is the most frequent complication of total thyroidectomy (transient form, 19-38%). Indocyanine green (ICG) fluorescence imaging is validated for parathyroid perfusion assessment; its predictive value combined with strict in situ preservation has not been reported in Romania. Objective:To evaluate the predictive performance of the Vidal Fortuny ICG score for transient postoperative hypoparathyroidism. Design:Prospective observational single-centre study (February 2024 - February 2025) at the National Institute of Endocrinology "C.I. Parhon", Bucharest. Subjects and methods:Twenty-four consecutive adults received intraoperative ICG (5 mg IV; Karl Storz IMAGE1 S™ Rubina®) during thyroid surgery. Each parathyroid gland (PG) was assigned an ICG score (0/1/2) and a signal-to-background ratio versus the common carotid artery. Primary endpoint: biochemical hypoparathyroidism at 24 hours (PTH < 15 pg/mL or total Ca < 8.0 mg/dL). Results:Twenty-one women and 3 men; mean age 55.2 ± 14.1 years. All four PGs were identified in every patient (96/96, 100%). Score distribution (score 2/ 1/ 0): 63.5%/ 32.3%/ 4.2%. Transient hypoparathyroidism: 25.0%; dysphonia at 6 weeks: 0%. Sensitivity 66.7%, specificity 100%, PPV 100%, NPV 90%; LR- 0.33 (LR+ undefined: specificity 100%). Conclusions:As an adjunct to careful anatomical dissection, the ICG score reliably identifies devascularized parathyroid glands (specificity and PPV both 100%). In situ preservation without autotransplantation was safe. ICG complements anatomical dissection and warrants routine integration.
Aim:This study examines the impact of liraglutide on bone turnover markers and bone mineral density (BMD) in individuals diagnosed with type 2 diabetes mellitus (T2DM). Patients and methods:A randomized controlled trial included 100 participants who were assigned to receive either liraglutide in combination with metformin (n=50) or metformin alone (n=50) for a duration of 48 weeks. Results:Analysis revealed statistically significant improvements in metabolic parameters, including glucose and lipid metabolism, in the liraglutide group compared to controls (P < 0.001). Notably, male participants exhibited enhanced bone turnover markers, evidenced by increases in N-terminal mid-region osteocalcin (N-MID) and total type I collagen amino-terminal propeptide (TPINP), alongside decreases in the C-terminal telopeptide of type I collagen (β-CTX). Conversely, female participants did not demonstrate significant changes in these markers. Additionally, liraglutide effectively mitigated BMD loss observed at the femoral neck and lumbar spine in the treatment group. These findings underscore liraglutide's potential benefits in metabolic regulation and its role in supporting bone health, particularly in male patients. Further research is essential to conclusively define these effects and elucidate the underlying mechanisms.
Objective:Graves' orbitopathy (GO) is an autoimmune inflammatory disorder characterized by proptosis, diplopia, and extraocular motility restriction. Intravenous glucocorticoids (IVGC) are the mainstay of treatment in active moderate-to-severe GO; however, some patients require additional therapy. This study compared the clinical outcomes of IVGC alone and in combination with orbital radiotherapy (RT) or mycophenolate mofetil (MMF). Methods:Forty patients with active moderate-to-severe GO (Clinical Activity Score ≥3) treated between 2015 and 2023 were included. Patients were grouped as IVGC monotherapy (n=24), IVGC+RT (n=8), and IVGC+MMF (n=8). Outcomes included CAS, proptosis (Hertel exophthalmometry), diplopia, and motility restriction at baseline and 6 months. Results:CAS significantly decreased in all groups (p<0.001). A ≥2-point reduction in CAS was observed in 91.7% of the IVGC group and in all combination therapy groups (p=1.000). Proptosis reduction ≥2 mm occurred in 57.1%, 100%, and 71.4% of patients in the IVGC, IVGC+RT, and IVGC+MMF groups, respectively (p=0.534). No statistically significant differences were detected in diplopia or motility outcomes between treatment groups. However, these findings should be interpreted cautiously given the limited sample size and unequal group distribution. Conclusion:IVGC effectively reduces disease activity in active moderate-to-severe GO. Although combination therapies showed numerically favorable trends in some outcomes, the retrospective design, unequal treatment allocation, and limited sample size preclude definitive conclusions regarding comparative efficacy between treatment strategies. Larger prospective studies are warranted to better delineate the role of combination approaches in active moderate-to-severe GO.
Small lymphocytic lymphoma (SLL) is an indolent lymphoma. Hypercalcemia is rarely associated with this type of lymphoma and was reported as a Richter`s transformation sign of SLL in the literature. We report a case of a 64-year-old man, with many comorbidities, including cardiac and renal pathologies, known with hepatitis B. Small lymphocytic B lymphoma with genetic risk factors, such as TP53, 17p and unmutated IGHV was diagnosed by laterocervical node biopsy. During chemotherapy, the patient initially presented sciatic pain, leading to the suspicion of a new associated malignancy, but the lumbar MRI excluded osteolysis. A few weeks later, the patient presented with neurological symptoms and dangerous hypercalcemia and high levels of iPTH were discovered. Parathyroid determination was discovered and the second line therapy with Venetoclax- Rituximab was chosen, but unfavorable evolution was noted, with activated macrophage syndrome, disseminated intravascular coagulation and multiple organ dysfunction syndrome. The genetic risk factors and the presence of hypercalcemia are markers of negative prognosis and unfavorable evolution of the disease.
Background:Polycystic thyroid disease (PCTD) is a recently defined entity, and its clinical significance has yet to be clarified in children. We aimed to investigate clinical and laboratory associations of PCTD. Methods:This study included 72 consecutive children diagnosed with PCTD. Auxological measurements, additional clinical diagnoses, ultrasonographic results as thyroid volumes, associated parenchymal diseases and solid nodules, serum thyroid hormone, and autoantibody levels, along with urinary iodine levels, were recorded. Results:Thirty-two male (mean age: 8.10±4.99 years) and 40 female (mean age: 9.51±4.68 years) patients were evaluated. No significant difference was found among the mean ages of gender groups (p= 0.22). Mean total thyroid volume was 5.49±4.1 mL and the mean colloidal cyst diameter was 4.36±2.34 mm among all participants. Colloidal cysts were found commonly in both thyroid lobes (90.5%). Solid nodules were found in 11% of the patients without a depicted malignant one. Initial thyrotropin (TSH) values were elevated in 29% (mean:10.89±4.66 mIU/L) of the patients, and initial free thyroxine (fT4) levels were normal in all participants. 31.9% of the patients underwent thyroid hormone replacement therapy with a mean L-T4 dosage of 20.01±9.02 μg/day during the follow-up. Conclusion:PCTD is an increasingly recognized radiological entity that frequently correlates with subclinical hypothyroidism in the pediatric population.
Background and Objective:Benign paroxysmal positional vertigo (BPPV) has been associated with low serum 25-hydroxyvitamin D levels and reduced bone mineral density (BMD), but it remains unclear whether these factors contribute to involvement of multiple semicircular canals. This study aimed to evaluate whether decreased BMD or vitamin D concentrations are associated with multi-canal BPPV. Methods:In this single-center retrospective study, 102 consecutive patients with idiopathic BPPV confirmed by video-oculography (VOG) were analyzed. All patients had serum 25-hydroxyvitamin D measurements and BMD T-scores assessed. Results:Among 102 patients (29 men, 73 women; mean age 62.3 ± 14.5 years), 70 had single-canal BPPV and 32 had multi-canal involvement. Mean vitamin D concentrations did not differ significantly between single-canal (24.52 ± 13.9 ng/mL) and multi-canal groups (19.55 ± 11.5 ng/mL; p = 0.0821). BMD T-scores were likewise similar (-1.93 ± 1.23 vs. -1.85 ± 1.34; p = 0.7639). Logistic regression showed that vitamin D insufficiency, vitamin D deficiency, osteopenia, and osteoporosis were not independent predictors of multi-canal BPPV. Conclusion:Low serum vitamin D levels and reduced BMD T-scores were not independently associated with multi-canal involvement in BPPV as confirmed by VOG diagnostics.
Background:Autoimmune thyroiditis, such as Graves' disease (GD) and Hashimoto's thyroiditis (HT), is a complex, genetically linked condition. IL-8 and TNF-α play a crucial role in these pathologies. Methods:This research was conducted on Tunisian patients with autoimmune thyroiditis (AITD) to examine the link between genetic variations in the IL-8 and TNF-α genes, their protein expression, and the likelihood of developing GD or HT. A total of 319 healthy controls, 230 patients with HT, and 75 patients with GD underwent genotyping via PCR-RFLP for the TNF-α-238 G/A and IL-8+781C>T polymorphisms. Plasma levels of IL-1β and TNF-α were also quantified. Results:The IL-8-781 T/T genotype and the IL-8-781 T allele were detected more frequently in HT and GD patients than in control participants. Patients with hypertension exhibited a higher frequency of the TNFA-238 G/A genotype and the TNFA-238 A allele compared to control individuals. However, no significant variation was observed in IL-8 and TNFA protein expression between patients and controls. Conclusions:The strong association between the IL-8-781C/T and TNFA-238 G/A polymorphisms and HT and GD suggests that these polymorphisms may play a crucial role in susceptibility to AITD within the Tunisian population.
Corticosteroids are systemically or locally used agents in treating many skin disorders. Besides their benefits within the correct indications, they may also increase many adverse reaction risks. Systemic absorption of topical glucocorticoids may rarely cause Iatrogenic Cushing Syndrome (ICS) in the geriatric population. On the other hand, to the best of our knowledge, ICS cases coexisting with pyoderma gangrenosum (PG) have not been reported before in the geriatric population. Herein, we aimed to present a 67-year-old female patient who developed ICS and was accompanied by PG due to long-term use of topical clobetasol 17-propionate therapy.
Context:Oxytocin (OXT) supports social affiliation and affect regulation; in late pregnancy, variability in plasma OXT may index the psychosocial context relevant to perinatal risk. Objectives:To test (i) differences in plasma OXT by adult attachment (AAS/R-AAS); (ii) associations with pregnancy planning, partner support, maternal perception, and history of emotional difficulties; and (iii) psychosocial factors independently associated with OXT. Design:Cross-sectional study. Subjects and Methods:Thirty-five women at 28-39 weeks' gestation (subsample of 140) provided morning EDTA plasma (08:00-10:00), stored at -80 °C. OXT was quantified by ELISA without solid-phase extraction or technical duplicates. Analyses comprised one-way ANOVA with Bonferroni tests, non-parametric contrasts (Mann-Whitney/Kruskal-Wallis with Holm adjustment), and HC3-robust multiple regression (α=0.05). Results:OXT differed by attachment (secure > avoidant > anxious-ambivalent; F(2,32)=31.115, p<0.001, ηp2=0.660). Univariate contrasts indicated higher OXT with planned pregnancy, partner support, positive (vs negative) maternal perception, and with a history of emotional difficulties; in the multivariable model (R2=0.718; adjusted R2=0.617), only attachment independently predicted OXT (avoidant vs secure B=-227.7 pg/mL; anxious-ambivalent vs secure B=-289.4 pg/mL). Conclusions:In late pregnancy, plasma OXT co-varies with adult attachment and, at group level, with proximal psychosocial factors; after adjustment, attachment remains the dominant predictor. Psychosocial screening is clinically actionable, whereas OXT measurement should remain a research tool.
Introduction:Sudden cardiac death (SCD) is a widespread and devastating event. As much as a quarter or half of all cardiovascular (CV) deaths are due to SCD. A lot of work is done to decrease the number of SCD. Recently several publications pointed out (very) high CV risk in Cushing's syndrome (CS) and CV risk is generally associated with SCD. Therefore, the aim of the study is to analyze the available publications regarding CS and SCD. Materials and methods:We initiated the search in SCOPUS using the terms "Cushing" and "sudden death". The additional documents were retrieved from Medline, Springer, SAGE, Science Direct, Cambridge, Wiley, PubMed, and Oxford Journals. There are no trials or registries published and therefore the narrative review is an appropriate approach to describe the problem, appraise the available evidence, and propose a solution. Results:There are four papers available from SCOPUS and four additional papers from other sources. The oldest paper on the topic is almost a century old (from 1927), the last one 33 years old, suggesting that this problem (SCD in CS) was not considered important for three decades. Therefore, a paucity of papers analyzed SCD risk in CS. We managed to identify several RFs of SCD that are prevalent in CS. Conclusion:Clustering of SCD risk factors suggest increased risk of SCD in Cushing disease (CD) and CS. The risk stratification tools for CV events should be studied, particularly so for SCD. Preventive measures should be tailored to the level of CV risk in individual CS patients. In addition, it carries a promise of prevention in individual patients, since SCD is preventable in part.
Objective:To probe into the potential connection between sarcopenia and insulin resistance in middle-aged and older cases with type 2 diabetes mellitus (T2DM). Methods:Ninety-six middle-aged and older patients with T2DM were selected. Bioelectrical impedance analysis was applied to take the appendicular muscle mass into measurement. Appendicular skeletal muscle mass index (ASMI) was calculated. By utilizing HOMA-IR and determining fasting C-peptide levels, insulin resistance (IR) was assessed. Results:According to the median value of ASMI (9.32 kg/m2), there were statistically significant differences in gender, height, weight, BMI, fasting C-peptide level, fasting glucose content in blood as well as in HOMA-IR among different ASMI groups. The correlated analysis unlocked that there were evidently negative correlations between ASMI and age, fasting blood glucose level (ρ=-0.214), lnHOMA-IR, and high-density lipoprotein dividly in middle-aged and older T2DM patients, while ASMI owned significantly positive correlation with fasting C-peptide level. In this population, male patients had a higher ASMI than females. After adjusting physical parameters and biochemical indicators, the multiple linear regression model demonstrated that ASMI was independently negatively correlated with lnHOMA-IR and fasting C-peptide level. Conclusion:ASMI associates with sarcopenia in middle-aged and older patients with T2DM is tightly linked with IR and pancreatic functionality.
Background and Objectives:Achieving optimal glycemic control in type 1 diabetes mellitus (T1DM) remains challenging despite the use of automated insulin delivery (AID) systems. This study evaluated glycemic outcomes and factors associated with poor control among T1DM patients using AID. Patients and Methods:A descriptive cross-sectional study was conducted among 23 patients with T1DM. Data included demographics, age at diagnosis, duration of AID use, hospitalization, and HbA1c levels. Glycemic control was classified as good (<7%) or poor (≥7%) according to ADA guidelines. Results:Participants were predominantly adults (82.6%), with a mean age of 23.9 ± 7.6 years, and mostly female (73.9%). The mean age at diagnosis was 10.3 ± 6.0 years. Poor glycemic control was observed in 78.3% of patients, with a mean HbA1c of 8.0 ± 1.7%. Better control was significantly associated with older age at diagnosis and AID use for 6-12 months (p < 0.05). HbA1c showed no significant correlations with age, age at diagnosis, or AID duration. Logistic regression identified younger age at diagnosis as the only independent predictor of poor glycemic control. Conclusion:Suboptimal glycemic control remains common among T1DM patients using AID systems. Early age at diagnosis is a key risk factor for poor outcomes.
Objective:Pituitary metastases are a rare entity, account for 1% of all intracranial metastases. This study aims to report a pituitary metastasis (PM) from bladder cancer and to provide a review of PM characteristics. Method:This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive literature search was performed using PubMed for studies published between January 2014 and January 2024. Results:One hundred twenty eight patients (66 females, 62 males) were identified in the literature over the past decade. Median age was 61 years. The most common primary malignancies were lung cancer (24.2%) and breast cancer (21.1%). The most common symptom was visual impairment (46.1%). Deficiencies in adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH) and gonadotropin hormones were diagnosed in 46%, 40.4%, 35% of cases, respectively. Diabetes insipidus (DI) was present in 33.6% of cases and panhypopituitarism was present in 21.9% of cases. PM management included transsphenoidal surgery alone (25%), transsphenoidal surgery combined with radiotherapy (16.4%), radiotherapy alone (10.2%), or observation without intervention (10.9%). The median survival following the diagnosis of PM was 6 months. Conclusion:While PM remain a infrequent entity, prolonged lifespan of cancer patients has led to increased detection. Patients frequently present with visual disturbance,diabetes insipidus and anterior pituitary hormone deficiency. No standardized treatment guidelines exist. Surgery and/or radiotherapy are used as palliative modalities rather than curative treatments. The prognosis is generally poor and is mostly related to the stage and type of the primary tumor.
Background:Growth hormone (GH) therapy is widely used for pediatric growth disorders, with short-acting (Saizen) and long-acting (Jintropin) formulations available. This study assesses height, weight, and bone age outcomes in children treated with Jintropin, Saizen, or a combination of both. Methods:This retrospective cohort study (N=108) compared Jintropin (n=31), Saizen (n=50), and Combination Therapy (n=27). To control for baseline heterogeneity (age, puberty) and repeated measures, analyses used ANCOVA and LMM. Post-hoc comparisons used Bonferroni correction. Safety was evaluated by ΔBA/ΔCA ratio. Results:Following multivariable LMM adjustment, the estimated marginal means for annualized GV were 9.30 cm/year (95% CI: 8.46-10.15) for Jintropin, 8.55 cm/year (95% CI: 7.90-9.20) for Saizen, and 9.56 cm/year (95% CI: 8.77-10.34) for Combination Therapy. Adjusted pairwise comparisons showed no significant efficacy differences between groups (Jintropin vs. Saizen: p=0.501; Combination vs. Saizen: p=0.160). Skeletal safety was confirmed across cohorts (ΔBA/ΔCA: 0.34, 0.46, 0.68), indicating no premature epiphyseal fusion. Conclusion:Long-acting Jintropin monotherapy provides growth outcomes comparable and non-inferior to daily Saizen, offering a convenient, effective alternative that reduces injection burden. The non-standard combination of long- and short-acting GH showed no statistically superior benefits, suggesting such complex regimens are unnecessary in clinical practice.
Background:In recent years, the incidence of thyroid cancer has been continuously increasing, which is in line with the prevalent trend of obesity. Objective:This study aims to investigate the relationship between obesity and BRAFV600E mutation. Methods:The study collected clinical and demographic data of 140 patients with papillary thyroid carcinoma. Statistical analyses included independent-samples t-tests, chi-square tests, and univariate and multivariable logistic regression analyses, as well as receiver operating characteristic (ROC) curve analysis. Results:The mean BMI was significantly higher in the BRAFV600E-positive group than in the negative group (p<0.001). BMI was independently associated with BRAFV600E mutation in both univariate (p=0.007) and multivariate analyses (p=0.026). ROC analysis demonstrated that BMI had modest predictive value (p=0.003). Research has observed the existence of sex differences, with a higher proportion of males in the BRAFV600E-positive group (p=0.047). Among BRAFV600E-positive patients, males had higher BMI and were more frequently classified as overweight or obese (P < 0.001). However, sex was not identified as an independent predictor in multivariate analysis. No significant associations were found between BRAFV600E mutation and Hashimoto's thyroiditis, diabetes, or fatty liver disease. Conclusion:This study demonstrates the association between higher BMI and BRAFV600E mutation in patients with PTC.
Introduction:Pseudohypoaldosteronism (PHA) is a rare condition that can lead to life-threatening hyperkalemia, cardiac arrest and death if not rapidly recognised and treated. Systemic PHA results from the inactivation of variants in genes encoding subunits of the epithelial sodium channel (ENaC). Frequent dose revision is required in oral replacement therapy in patients with systemic PHA. This condition requires a lifelong close follow-up and treatment process in patients. Case Description:In this study, we present the clinical follow-up of a newborn diagnosed with PHA who presented at 9 days of age with severe dehydration, malnutrition, vomiting and lethargy. A novel pathogenic homozygous mutation, c.1536C>A p.(Tyr512*), was identified in exon 11 of the SCNN1A gene. Discussion:Systemic PHA is a rare, life-threatening disorder that may be misdiagnosed in early infancy. Our case highlights a severe systemic presentation associated with ENaC dysfunction. Reporting the clinical course together with genetic findings may improve recognition of severe phenotypes, support earlier diagnosis, and contribute to a better understanding of genotype-phenotype relationships in systemic PHA. Conclusion:Neonates with hyperkalemia and hyponatremia should prompt suspicion of PHA and early aggressive treatment; this case highlights severe systemic PHA and the importance of combined clinical and genetic evaluation.
