Search Results (345)

In Pteropus spp., metabolic bone disease has been consistently associated with fruit-based diets that are deficient in calcium, vitamin D precursors, and protein, as well as limited ultraviolet B (UVB) exposure, as reported in zoological surveys and clinical observations. Comparative mammalian physiology suggests that dysregulation of the endocrine axis involving parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcitonin, and calcitriol may contribute to disease development, although direct species-specific endocrine data in flying foxes remain scarce. This narrative review synthesizes current knowledge from published zoological reports, clinical observations, and comparative mammalian physiology regarding the etiology, pathophysiology, and clinical expression of metabolic bone disease in captive flying foxes. Much of the available evidence is derived from juvenile Pteropus vampyrus, and its applicability to other Pteropus species remains to be fully established. The limited availability and consistency of existing data, together with the scarcity of controlled experimental and longitudinal studies, necessarily constrain the conclusions that can be drawn. Nevertheless, this review highlights key nutritional and environmental risk factors and summarizes evidence-informed preventive management strategies to improve skeletal health and welfare in managed Pteropus populations. Full article

Purpose: Hyperparathyroidism (HPT) is a condition marked by excessive secretion of parathyroid hormone (PTH), leading to disturbances in calcium, phosphate, and vitamin D metabolism. HPT is classified into primary (pHPT), secondary (sHPT), and tertiary (tHPT) types, which can cause systemic complications. Parathyroidectomy (PTX) remains the cornerstone treatment for pHPT and refractory cases of sHPT and tHPT. Methods: A retrospective review was conducted on 10 pediatric patients who underwent PTX for HPT at our clinic between 2016 and 2024. Demographic data, preoperative imaging, laboratory findings, surgical details, pathology reports, and postoperative outcomes were analyzed. Patients were categorized as having either pHPT (n = 6) or renal HPT (r-HPT; n = 4), which included one case of sHPT and three cases of tHPT. Results: The mean age of pHPT and r-HPT patients was 15 and 13 years, respectively. While 50% of pHPT patients were female, all r-HPT patients were female. Preoperative imaging localized parathyroid lesions using ultrasonography in all cases, but Sestamibi scintigraphy had a lower detection rate (66.7%). Minimally invasive parathyroidectomy was performed in single-gland pHPT cases, while bilateral neck exploration was used for multiglandular pHPT and all r-HPT cases. No intraoperative complications were observed. Postoperatively, all patients demonstrated normalized calcium, phosphate, and PTH levels with significant symptomatic improvement. Hungry bone syndrome developed in one r-HPT patient and was managed successfully. No recurrences were noted during an average follow-up of 39 months. Conclusions: PTX is a safe and effective treatment for pediatric HPT, providing excellent biochemical and clinical outcomes. Multidisciplinary collaboration is crucial in managing pediatric cases, particularly those with complex renal HPT. Full article

Hyperparathyroidism is a serious complication of chronic kidney disease (CKD) and can occur in patients not on renal replacement therapy, during dialysis therapy, or after kidney transplantation. The disease leads to an increased risk of cardiovascular events, bone loss, and fractures. Cinacalcet is a widely used drug, but its effectiveness in treating hyperparathyroidism in selected stages of chronic kidney disease remains unclear. This critical review aims to integrate findings from meta-analyses and clinical trials to assess optimal therapeutic strategies in patients suffering from CKD, who are non-dialysis-dependent, dialysis-dependent, and after kidney transplantation. The authors reviewed eligible studies, including meta-analyses, randomized controlled trials, and observational studies assessing biochemical outcomes, cardiovascular, bone, and survival outcomes with cinacalcet. Cinacalcet effectively reduced serum parathyroid hormone (PTH), calcium, and phosphorus across all CKD stages, particularly in hemodialysis patients. Combination therapy with vitamin D analogs enhanced biochemical control without increasing adverse events, although mild, transient hypocalcemia and gastrointestinal symptoms were common. In kidney transplant recipients, parathyroidectomy achieved greater normalization of PTH and calcium. Cinacalcet has been shown to reduce mortality in patients on hemodialysis and peritoneal dialysis. Full article

Background and Objectives: Vascular calcification (VC) is a major contributor to cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), particularly those on hemodialysis. Once considered a passive process, VC is now recognized as an active, cell-mediated pathology influenced by mineral dysregulation, chronic inflammation, and oxidative stress. This review aims to synthesize current evidence on the underlying mechanisms of VC in CKD and hemodialysis, with particular focus on emerging biomarkers and therapeutic implications. Materials and Methods: A structured narrative review was conducted by searching PubMed, Web of Science, ScienceDirect, and Google Scholar. The final search was completed on 29 August 2025. A total of 1326 articles were initially retrieved, of which 65 met the inclusion criteria and were analyzed. Studies addressing VC mechanisms, the bone–vascular axis, mineral metabolism, vitamin K–dependent proteins, and biomarkers such as matrix Gla protein (MGP), osteocalcin (OC), and intact parathyroid hormone (iPTH) were included. Results: VC in CKD arises from phenotypic transformation of vascular smooth muscle cells, vesicle-mediated calcification, oxidative stress, and impaired activity of endogenous calcification inhibitors. Disruption of the fibroblast growth factor 23 (FGF23)–Klotho axis and secondary hyperparathyroidism further exacerbate vascular pathology. Among emerging biomarkers, dp-ucMGP reflects vitamin K deficiency and correlates with calcification burden, while OC and iPTH provide insight into bone–vascular crosstalk and mineral turnover. However, biomarker interpretation is limited by assay variability, renal clearance, and clinical heterogeneity. Conclusions: VC in CKD represents a complex process driven by systemic and cellular dysregulation. While biomarkers such as dp-ucMGP, OC, and iPTH offer mechanistic insights and prognostic potential, further validation is required for clinical application. A multimarker approach, combined with individualized management of mineral metabolism, may improve risk stratification and therapeutic targeting in this high-risk population. Full article

Parathyroid carcinoma (PC) is an exceedingly rare endocrine malignancy, accounting for less than 1% of all primary hyperparathyroidism (pHPT) cases. It typically presents with pronounced hypercalcemia and markedly elevated parathyroid hormone (PTH) levels. Accurate imaging plays a pivotal role in diagnosis, staging, surgical planning, and long-term surveillance, although differentiating PC from benign disease on imaging remains a significant challenge. A multimodal imaging strategy combining cervical ultrasonography (US) and nuclear medicine techniques provides high sensitivity for lesion detection. Ultrasonography with advanced detective flow imaging allows detailed anatomical assessment and evaluation of vascular patterns of the primary tumor. [^99mTc]Tc-methoxyisobutylisonitrile ([^99mTc]Tc-MIBI) scintigraphy frequently demonstrates prolonged tracer retention in PC, while [¹⁸F]fluorocholine positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance (PET/MR) imaging have shown superior performance for detecting both primary tumors and metastatic disease due to its higher spatial resolution and higher molecular sensitivity. [¹⁸F]FDG PET serves as an adjunct modality for identifying aggressive, metabolically active lesions. Emerging radiotracers such as [¹⁸F]-fibroblast activation protein inhibitor ([¹⁸F]FAPI) and [⁶⁸Ga]Ga-trivehexin have shown potential in cases where initial imaging is inconclusive. Theranostic strategies that integrate molecular imaging with targeted radioligand therapy may transform PC management by enabling personalized treatment approaches tailored to each tumor’s biological and imaging characteristics. This review aims to evaluate available imaging modalities for PC diagnosis and provide guidance for their clinical application. Full article

The thymus and parathyroid glands share a common embryological origin from the third pharyngeal pouch, yet their potential morphological and functional interconnections remain insufficiently explored. We conducted a comparative study integrating immunohistochemistry (IHC) and SEM on human thymic tissue, parathyroid adenomas, and parathyroid tissue excised during thyroidectomy. IHC staining targeted Thymosin-α1, CaSR, and PTH1R, with semi-quantitative evaluation of staining intensity and distribution. SEM analysis was performed at multiple magnifications to assess stromal organization and microvascular relief. Non-parametric statistical tests (Kruskal–Wallis with Mann–Whitney post hoc comparisons) were applied to clinical and laboratory data across the three cohorts. Scanning electron microscopy (SEM) revealed convergent ultrastructural features between thymus and parathyroid, including reticular stromal meshes and vascular grooves suggestive of comparable microcirculatory organization. IHC demonstrated robust Thymosin expression in thymus, with heterogeneous/apical distribution in parathyroid tissue; CaSR showed strong membranous and cytoplasmic expression in parathyroid, but weak diffuse signal in thymus; PTH1R exhibited low-to-moderate expression in thymus and moderate heterogeneous expression in parathyroid, with apical accentuation in adenomas. Statistical analysis confirmed significant differences in ionized calcium, PTH, and anti-AChR titers among the three cohorts (all p < 0.001), while TSH and calcitonin did not differ significantly. Our findings strengthen the hypothesis of a morpho-functional parathyroid–thymus axis. The robust parathyroid expression of CaSR and PTH1R aligns with established roles in calcium–PTH homeostasis, while the novel detection of Thymosin in parathyroid tissue suggests an expanded functional repertoire. These results highlight a continuum between embryological proximity and adult tissue cross-talk, with potential clinical implications for parathyroid pathology and immune regulation. Full article

Type 2 diabetes (T2D) is associated with normal or higher bone mineral density (BMD), but there is a higher fracture rate. Hypoglycaemia does not affect BMD but may cause fractures directly through falls and may affect bone cellular metabolism. We examined circulating bone marker proteins (BMPs) in response to induced hypoglycaemia in T2D versus controls. A prospective exploratory parallel study design was conducted in T2D patients (n = 23) and healthy controls (n = 23) who underwent blood SOMAscan proteomic analysis of bone biomarkers at baseline, hypoglycaemia, and post-hypoglycaemia time points. Unadjusted repeated measures linear mixed modeling was used for analysis. Linear mixed modeling of the proteins showed that the way most BMPs changed over time did not differ between groups. At baseline, Dickkopf-related protein 1 (DKK1), cathepsin A, cathepsin S, and cathepsin Z were increased in T2D versus controls (p < 0.05), whilst fibroblast growth factor 23 (FGF23) was lower in T2D versus controls (p ≤ 0.05). Following hypoglycemia, transient changes from baseline occurred in DKK1, cathepsin A, cathepsin G, cathepsin H, cathepsin S, cathepsin Z, parathyroid hormone (PTH), Sphingosine kinase 1 and 2 (SPK1/2), and interleukin-1 beta (IL1 beta) over the post-hypoglycaemia time course. There was decreased cathepsin S in T2D from baseline to 24 h compared to the control group, and increased cathepsin Z at 24 h for both groups overall compared to baseline (p < 0.05). Baseline-raised cathepsins (A, S, Z) in T2D may enhance osteoclastic resorption, whilst raised DKK1 could inhibit osteoblast differentiation and suppress bone formation. Hypothetically, this may lead to a decline in bone quality through a resorption-enhanced, low bone formation imbalance. The effects of hypoglycaemia on bone physiology appear to extend significantly beyond the initial insult, as seen for cathepsin S and Z, which differed at 24 h compared to baseline. Full article

Background: Metabolic bone disease (MBD) of prematurity predisposes extremely preterm and extremely low birth weight (ELBW) infants to atraumatic fractures. Evidence on fracture reduction after structured Bone Health Programs (BHPs) remains limited. Methods: We conducted a single-center retrospective cohort of NICU admissions (2014–2024) with gestational age < 28 weeks and/or birth weight < 1000 g, comparing a pre-program era with a standardized BHP that incorporated protocolized biochemical surveillance, a week 4 screening radiograph, optimized mineral targets, pharmacist review of parenteral minerals, and “handle-with-care” practices. The study aimed to evaluate whether implementation of a structured BHP reduced fracture incidence and improved biochemical and clinical outcomes in extremely preterm and ELBW infants. Prespecified effect measures were risk ratio (RR), risk difference (RD) with 95% confidence intervals, Fisher’s exact p values, and number needed to treat (NNT). Among infants with fractures, we compared clinical course and biochemical context across eras. Results: Of 708 eligible infants, 221 were born pre-program and 487 post-program with similar baseline characteristics. Fracture incidence decreased from 9.5% (21/221) to 1.64% (8/487); RR 0.17 (95% CI 0.08–0.38); RD −7.86 percentage points; p < 0.001; NNT ≈ 13. Among infants who fractured, length of stay was lower post-program (104.1 ± 28.3 vs. 172.0 ± 91.5 days). Peak alkaline phosphatase and parathyroid hormone were also lower in the post-program era (ALP 501.3 ± 71.2 vs. 972.5 ± 93.5 IU/L, p = 0.032; PTH 23.1 ± 12.5 vs. 38.4 ± 21.7 pmol/L, p = 0.027), whereas serum phosphate and 25 OH vitamin D did not differ significantly. The fracture burden per infant decreased following the BHP (1.50 ± 0.53 vs. 3.19 ± 3.08, p = 0.024). Age at first fracture was earlier post-program, consistent with scheduled imaging (48.4 ± 34.9 vs. 83.9 ± 37.3 days, p = 0.031). Conclusions: A structured BHP was associated with a large reduction in fracture incidence and more favorable biochemical profiles, together with shorter hospitalization among fracture cases. Program elements that combine scheduled imaging, biochemical triggers, nutritional optimization, parenteral mineral stewardship, and standardized handling may improve skeletal outcomes. Multicenter prospective evaluations should confirm generalizability and define core components. Full article

Recent progress in laboratory medicine provides powerful tools for the detailed evaluation of cardiovascular risk in military populations. This study aimed to characterize cardiometabolic biomarker profiles across four Polish military groups through chemometric analysis. The study included 392 participants (336 men, 56 women, aged 19–56 years). In total, 23 serum biomarkers from lipid, metabolic, hepatic, hormonal, and bone axes, and lactate dehydrogenase (LDH) were analyzed. Random forest (RF) modeling and effect-size profiling identified group-specific signatures. Group 4 (exposed to extreme acceleration forces and ionizing radiation) exhibited a systemic stress and metabolic-load profile with higher N-terminal pro-B-type natriuretic peptide (NT-proBNP, 36.7 ± 48.2 pg/mL) and calcium (Ca, 10.4 ± 0.88 mg/dL), and lower parathyroid hormone (PTH, 15.4 ± 10.1 pg/mL) and C-terminal telopeptide of type I collagen (β-CTX, 0.22 ± 0.19 ng/mL). Group 2 (exposed to fuels and exhaust gases) and group 3 (exposed to vibration, noise, ionizing radiation) showed an atherogenic–hepatometabolic axis with elevated apolipoprotein B (apoB, 1.04 ± 0.31; 0.97 ± 0.29 g/L), non-high-density lipoprotein cholesterol (N-HDL, 151.0 ± 46.7; 147.0 ± 41.4 mg/dL), and alanine aminotransferase (ALT). Group 1 (exposed to a biological hazard) displayed higher glucose (Glu, 96.0 ± 25.6 mg/dL) and triglycerides (TG, 151.0 ± 113.0 mg/dL) with lower magnesium (Mg, 2.03 ± 0.27 mg/dL). RF modeling confirmed these constellations. This study was exploratory in nature, providing a foundation for future longitudinal research. These findings provide a rationale for tailored cardiovascular surveillance, although causal inference is limited by the cross-sectional design. Full article

(1) Background: this study aimed to determine whether a serum parathyroid hormone (PTH) threshold of 40 pg/mL represents a clinically relevant risk factor for vitamin D (VitD) deficiency and reduced bone mineral density (BMD). It also investigated potential genetic interactions influencing PTH regulation and skeletal health in patients with periodontitis. (2) Methods: a cross-sectional analysis was conducted on 1038 periodontitis patients (35–75 years). Serum PTH, VitD, calcium (Ca), phosphate (P), and urinary parameters were assessed. Dual-energy X-ray absorptiometry (DXA) was used to evaluate BMD in 261 subjects. Vitamin D Receptor (VDR) and estrogen receptor alpha (ERα) polymorphisms were genotyped, and composite genetic risk scores were calculated. Statistical analyses included correlation tests, subgroup comparisons, and regression models. (3) Results: sixty-two percent of individuals had PTH > 40 pg/mL, which was associated with significantly lower 25(OH)D and Ca levels and reduced T-scores (p < 0.05). PTH levels negatively correlated with BMD (Pearson’s r = –0.159, p = 0.0105). Patients with higher ERα polymorphism scores showed increased PTH values (p < 0.05), while VDR variants demonstrated a positive but no significant trend. (4) Conclusions: a PTH threshold of 40 pg/mL identifies individuals at higher risk of VitD deficiency and skeletal fragility, even without overt hypercalcemia. Genetic factors, particularly ERα variants, may contribute to elevated PTH levels, suggesting value in integrating biochemical, densitometric, and genetic screening for early bone health risk stratification. Full article

Background/Objectives: Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome caused by phosphaturic mesenchymal tumors (PMTs). FGF23, which is overproduced by PMTs, causes hypophosphatemia and osteomalacia, ultimately leading to multiple insufficiency fractures, which are the cause of TIO symptoms. Therefore, recovery from TIO symptoms often takes several months. Due to its paracrine effects, even minuscule amounts of residual PMT can cause treatment to fail. To further compound this, the most confident methods for residual PMTs, serum FGF23 level and ⁶⁸Ga DOTA-based PET/CT, are not readily available. For these reasons, there is currently no established method for early prediction of TIO treatment outcomes after surgery. This study focuses on mineral metabolism and bone turnover markers to identify a clinically practical and readily available biomarker that can predict TIO treatment outcomes. Methods: During treatment, we analyzed repeated measurements during treatment of mineral metabolism and bone turnover markers for 19 cases of TIO—Ca, inorganic phosphate (Pi), parathyroid hormone (PTH), 25-hydroxyvitamin D, alkaline phosphatase, Procollagen 1 N-terminal Polypeptide, and β-CrossLaps—in relation to treatment outcomes. We selected predictive marker candidates from among these markers by analyzing their patterns of change during treatment based on three viewpoints—association with (1) cure status, (2) time after treatment, and (3) the interaction effects between (1) and (2) using Linear Mixed Model analysis. We also validated the predictive performance of the selected candidates. Results: In long-term follow-up, only serum Pi and PTH levels were significantly associated with all three metrics mentioned above, suggesting that their patterns of change reflect the clinical course and results of TIO treatment. Pi was the only marker that displayed the same associations during short-term follow-up (two weeks and six weeks after treatment), suggesting that it is a rapidly responsive marker. The serum Pi level two weeks after treatment (Odds Ratio = 7.314, p = 0.028, AUC value of 0.907) and the normalization of Pi at two weeks post-treatment (Relative Risk = 9.975, p = 0.010; sensitivity = 100.0% [95% Confidence Interval (CI) 0.860 to 1.000], specificity = 60.0% [95% CI, 0.208 to 0.600]) were both significantly associated with a complete cure. Conclusions: Serum Pi is a fast, simple, and highly sensitive marker that can replace serum FGF23 and ⁶⁸Ga DOTA-based PET/CT in clinical practice for predicting a complete cure of TIO within two weeks of surgery. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) affects 30–50% of end-stage renal disease patients. Parathyroidectomy (PTX), while effective for medication-refractory SHPT, carries 20–70% risk of hungry bone syndrome (HBS)—severe sustained hypocalcemia requiring intensive care and prolonged hospitalization. Accurate preoperative risk stratification using biochemical markers and validated prediction tools is critical for optimal preventive management. Methods: We conducted a comprehensive narrative review synthesizing evidence on HBS predictors after PTX in SHPT, evaluating traditional and novel bone turnover markers, clinical risk factors, and multivariate prediction models, through a structured literature search and analysis. Results: Preoperative bone turnover status represents the strongest contributor to HBS risk. Traditional biomarkers—particularly parathyroid hormone (PTH > 1000–2400 pg/mL) and alkaline phosphatase (ALP > 150–300 U/L)—demonstrate moderate-to-strong individual predictive power. Novel bone turnover markers (bone-specific ALP, P1NP, TRAP-5b) offer incremental value, especially in CKD populations where renal clearance affects traditional markers. Combined risk prediction models substantially outperform single biomarkers, achieving area under curve values of 0.87–0.95. The simple NYU 2-point score (ALP > 150 U/L + PTH > 1000 pg/mL) showed 96.8% accuracy, with 100% negative predictive value. More complex tools like nomograms (C-index 0.92–0.94) and machine-learning algorithms (AUC 0.88) provide enhanced discrimination by integrating multiple continuous parameters. Additional clinical factors—younger age (<48 years), prolonged dialysis (≥5 years), low preoperative calcium, high gland weight, and absence of autotransplantation—further refine risk assessment. Postoperative calcium typically reaches nadir at 48–72 h, defining the critical monitoring window. Conclusions: High-turnover bone biomarkers and combined risk models effectively identify high-risk SHPT patients. Risk-stratified protocols (i.e., prophylactic supplementation, intensive monitoring, and selective ICU admission) can substantially reduce HBS-related morbidity. Ongoing efforts should focus on validating these predictive tools across diverse populations and integrating them into clinical practice, thereby facilitating real-time HBS risk assessment and protocol-driven care. Full article

Parathyroid gland disorders, including secondary hyperparathyroidism, have emerged as significant endocrine complications in people living with HIV (PLWHIV). This narrative review synthesises recent evidence on the prevalence, mechanisms, and clinical implications of parathyroid dysfunction in PLWHIV. HIV infection, combined antiretroviral therapy (cART), and immune activation contribute to parathyroid dysfunction, with cART regimens, particularly Tenofovir Disoproxil Fumarate (TDF), exacerbating these disturbances by altering the calcium and parathyroid hormone (PTH) dynamics. Studies show that PTH levels in PLWHIV on TDF were significantly elevated compared to those on non-TDF-based cART regimens. Histopathological studies highlight a higher prevalence of parathyroid hyperplasia in PLWHIV, often linked to chronic deficiencies in calcium, magnesium, and vitamin D, as well as immune dysregulation. The dysfunction observed ranges from inappropriate elevation of PTH levels to hypoparathyroidism, leading to rapid bone density loss and an increased fracture risk. Despite the fact that HIV is a condition associated with high malignancy, parathyroid malignancy is a very rare issue. Despite the growing recognition of these complications, routine screening for PTH and bone health remains inadequate in standard clinical HIV care. This review advocates for incorporating routine monitoring of serum PTH, calcium, phosphate, and vitamin D levels, especially in those on TDF-based cART. Early detection of subclinical parathyroid dysfunction can prevent complications such as secondary hyperparathyroidism and neuromuscular symptoms. Clinicians should be aware of atypical biochemical presentations, such as elevated PTH with normal calcium, which may indicate cART-induced dysregulation, improving patient management and outcomes. Full article

Background: Hypercalcemia is a common and serious complication of malignancy, often contributing to morbidity and mortality. In patients with paraproteinemia, elevated total calcium with normal ionized calcium, termed pseudohypercalcemia, can complicate diagnosis and lead to inappropriate treatment. While this phenomenon has been described in case reports, its prevalence and clinical impact in routine practice remain poorly defined. Methods: We report a case of pseudohypercalcemia in a patient with IgG κ multiple myeloma and conducted a retrospective review of de-identified data to assess the prevalence and biochemical associations of pseudohypercalcemia in paraproteinemia. Available data included serum protein electrophoresis (SPEP), total calcium, albumin, total protein, creatinine, and parathyroid hormone (PTH). Associations between calcium status, paraprotein levels, and the gamma globulin gap were examined. Results: The index case demonstrated pseudohypercalcemia, with elevated total calcium (13.5 mg/dL) but normal ionized calcium (1.22 mmol/L), in the setting of IgG κ paraproteinemia (4.4 g/dL). In the retrospective cohort of 2537 samples, 986 (39%) had a single monoclonal paraprotein. Gamma globulin gap showed a moderate correlation with paraprotein concentration for IgG (r = 0.56, p < 0.0001) and IgA (r = 0.44, p < 0.0001), but a weaker relationship for IgM (r = 0.49, p < 0.0001). In contrast, total calcium showed no significant correlation with paraprotein concentration in the overall cohort. Among samples with elevated calcium (>10.5 mg/dL), the association between calcium and IgG paraprotein levels remained weak (r = 0.34, p = 0.23), and was similar for IgG κ (r = 0.61, p = 0.12) and IgG λ (r = 0.09, p = 0.87). Hypercalcemia was uncommon, occurring in only ~2% of IgG-positive samples, and rarely at paraprotein levels ≥ 1.5 g/dL. Conclusions: Pseudohypercalcemia in paraproteinemia is uncommon but clinically important, as total calcium may be artifactually elevated due to paraprotein-related assay interference, either from assay precipitation effects or calcium binding by paraproteins. Paraprotein burden correlates with gamma globulin gap but not with true calcium status. Reliance on total calcium alone may lead to diagnostic misclassification; ionized calcium should be measured in patients with monoclonal gammopathies to distinguish true hypercalcemia from analytical interference and avoid unnecessary treatment. Full article

Tertiary hyperparathyroidism (THPT) arises in patients with chronic kidney disease (CKD) as a consequence of prolonged secondary hyperparathyroidism and is marked by autonomous parathyroid hormone (PTH) secretion. In some cases, parathyroid hyperplasia persists even after successful renal transplantation, resulting in sustained PTH elevation and hypercalcaemia. These alterations contribute to bone loss, vascular calcification, and increased cardiovascular risk. Management includes medical therapy with calcimimetics or vitamin D analogues and surgical intervention via parathyroidectomy. However, optimal timing and treatment strategy remain uncertain. This review examines the pathophysiology, clinical manifestations, and current management paradigms of THPT, with an emphasis on areas that require further research and consensus. Full article