Search Results (286)

Purpose: This study investigates the role of CASR gene polymorphisms (A986S, R990G, Q1011E) in PHPT genetic susceptibility and its clinical variability. The aim is to evaluate the prevalence of these polymorphisms in patients with sporadic PHPT and their impact on clinical course, biochemistry, and histological features. Methods: 106 patients underwent clinical and anamnestic evaluations, focusing on major PHPT complications, as well as biochemical analyses of blood and urine. Genetic testing was conducted for CASR gene polymorphisms. Histological data were available for 68 patients who underwent parathyroidectomy. Results: The sample included 83 women and 23 men; mean age at diagnosis was 54.5 years. 55 patients carried CASR gene polymorphisms, while 51 were wild-type. Prevalence rates of polymorphisms were consistent with data for the Caucasian population, with A986S being the most common (31%). No significant associations were found between polymorphisms and increased levels of ionized calcium or other blood phospho-calcium metabolism parameters. However, 24-h urinary calcium levels were higher in patients with polymorphisms (p = 0.0185), particularly in those older than 50 years (p = 0.030) and with the A986S variant. Hypercalciuria was predictive of CASR polymorphism presence (OR = 2.76, p = 0.003). No significant association with PHPT complications, such as renal calculi or bone involvement, was confirmed. Histological data revealed no clear links between polymorphisms and more aggressive variants. Conclusions: CASR gene polymorphisms are associated with hypercalciuria but do not significantly influence age of onset or clinical phenotype in PHPT. Genetic analysis may be useful in selected cases to better understand individual clinical profiles. Full article

The jaw bones can manifest various cysts and tumors of different origins and etiologies. Any bone lesions lacking any potential odontogenic origin might require more accurate diagnostics, adequate investigation, and careful patient anamnesis. In cases of sharply demarcated radiolucency or mixed radiolucent–radiopaque radiological appearance lesions, they can sometimes extend between the displaced tooth roots or cause their resorption. The scope of cortical bone in radiographic studies might have a different status, and lesions can spread outside of the bone. If no odontogenic feature is present, an additional blood examination for bone markers and calcium–phosphate markers is useful to establish any endocrine-related pathologies. In the primary hyperparathyroidism (PHP), bone blood markers and bone scintigraphy are very useful to establish the possible occurrence of brown tumor. On the other hand, in central giant cell granuloma (CGCG), only a direct tumor lesion biopsy might confirm the diagnosis, where in microscopic evaluation, mostly fibroblasts and secondary cells have multinucleated giant cells along with some accessory cells like macrophages, dendrocytes, and other endothelial cells. Because both lesions can have similar clinical and radiological appearances and unclear borders, with different shapes, sizes, and symptoms, it is quite important to compare both clinical and radiological patient characteristics. The authors aim to present how radiological studies alone can easily lead to lesion misdiagnosis. They also aim to emphasize how local treatment methods without advanced microsurgical reconstruction can, in some cases, improve patient outcomes. Full article

Background/Objectives: Brown tumors are bone manifestations of hyperparathyroidism, and they are characterized by histologic similarities with Central Giant Cell Granuloma (CGCG). Their diagnosis requires clinical, microscopic, macroscopic, and serologic correlation, as there is usually an elevation in parathormone levels due to the underlying metabolic disorder. Methods: This case describes a patient with a left mandibular lesion and a history of CGCG. Results: Through the joint analysis of clinical, histologic, and serologic findings, the diagnosis of a brown tumor associated with hyperparathyroidism was confirmed. Conclusions: This case highlights the importance of a comprehensive evaluation of oral and systemic features for accurate diagnoses and appropriate patient management. Full article

Introduction: Primary hyperparathyroidism (pHPT) is an endocrine disorder characterized by excessive parathyroid hormone production, typically due to adenomas, hyperplasia, or carcinoma. Preoperative imaging plays a critical role in guiding surgical planning, particularly in selecting patients for minimally invasive procedures. While first-line imaging techniques, such as ultrasound and 99mTc-sestamibi scintigraphy, are standard, advanced second-line imaging modalities like 18F-fluorocholine PET/CT (FCH-PET) and four-dimensional computed tomography (4D-CT) have emerged as valuable tools when initial diagnostics are inconclusive. Methods: This article provides an updated review and recommendations of the role of these advanced imaging techniques in localizing parathyroid adenomas. Results: FCH-PET has shown exceptional sensitivity (94% per patient, 96% per lesion) and is particularly useful in detecting small or ectopic adenomas. Despite its higher sensitivity, it can yield false positives, particularly in the presence of thyroid disease. On the other hand, 4D-CT offers detailed anatomical imaging, aiding in the identification of parathyroids in challenging cases, including recurrent disease and ectopic glands. Studies suggest that FCH-PET and 4D-CT exhibit similar diagnostic performance and could be complementary in preoperative planning of most difficult situations. Conclusions: This article also emphasizes a multimodal approach, where initial imaging is followed by advanced techniques only in cases of uncertainty. Although 18F-fluorocholine PET/CT is favored as a second-line option, 4D-CT remains invaluable for its high spatial resolution and ability to guide surgery in complex cases. Despite limitations in evidence, these imaging modalities significantly enhance the accuracy of parathyroid localization, contributing to more targeted and minimally invasive surgery. Full article

Background and Clinical Significance: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare autosomal dominant disorder caused by mutations in the MEN1 gene. Although primarily characterized by endocrine tumors, renal manifestations remain underreported. Case Presentation: We report a three-generation family carrying a pathogenic MEN1 mutation (c.1351-3_1359del) with a co-occurring Claudin 16 (CLDN16) variant (c.324+13C>G). Genetic testing included MLPA and whole-exome sequencing (WES), with bioinformatics analysis validating variant pathogenicity. All three patients exhibited primary hyperparathyroidism, hypercalcemia, hypercalciuria, early nephrocalcinosis, and renal hypomagnesemia. The CLDN16 variant, previously considered benign, co-segregated with hypomagnesemia and renal involvement, suggesting a potential modifying role. Conclusions: These findings support the need for comprehensive genetic screening in MEN1 patients with atypical renal presentations. Concomitant genetic variations can alter the principal phenotype. Full article

Synchronous multiple parathyroid carcinoma is a rare condition within the already uncommon landscape of parathyroid malignancies, which comprise less than 1% of sporadic primary hyperparathyroidism cases. To date, only seven cases of synchronous multiple parathyroid carcinoma in sporadic primary hyperparathyroidism have been documented. This exceptional rarity complicates both the diagnostic process and therapeutic decision-making. Clinically, parathyroid carcinoma typically presents as a single mass determining severe symptoms. However, no single clinical, biochemical, or imaging feature allows for definitive preoperative diagnosis. Imaging modalities such as ultrasound and sestamibi scans exhibit variable sensitivity and may overlook multi-gland involvement. Histopathological examination remains the only reliable diagnostic method. Management strategies are also controversial: while some advocate for conservative surgery, en bloc resection is generally recommended for its association with improved local control and disease-free survival. Given the exceptional occurrence of synchronous multiple parathyroid carcinoma, there is a lack of standardized protocols for managing parathyroid carcinoma in cases of synchronous and multiple gland involvement. Early multidisciplinary evaluation and individualized treatment planning are therefore crucial. This review aims to synthesize the presently available knowledge about synchronous multiple parathyroid carcinoma, assist clinicians with the limited data available, and discuss the main challenges in the management of this rare entity. Full article

Background/Objectives: Secondary hyperparathyroidism (SHPT) is a prevalent complication in end-stage renal disease, often necessitating surgical intervention when refractory to medical therapy. The optimal surgical strategy—subtotal parathyroidectomy (SPTX) versus total parathyroidectomy with/without autotransplantation (TPTX ± AT)—remains debated, especially considering postoperative complications like persistent HPT and hungry bone syndrome (HBS). This study aimed to compare early surgical outcomes and identify predictors for postoperative complications in patients undergoing SPTX and TPTX + AT. Methods: We conducted a retrospective, single-center observational study involving 93 dialysis patients who underwent PTX for drug-refractory SHPT. Patients were analyzed according to surgical procedure (SPTX vs. TPTX + AT), focusing on postoperative complications such as cervical bleeding, reintervention rates, and the incidence of HBS. Multivariate logistic regression was utilized to identify predictors of these outcomes. Results: TPTX + AT demonstrated superior control of HPT, with significantly lower rates of reintervention compared to SPTX (7.1% vs. 23.5%, p = 0.037). However, TPTX + AT was associated with a higher incidence of HBS (57.1% vs. 35.3%, p = 0.039). Independent predictors of reintervention included absence of concomitant thymectomy, preoperative hypercalcemia, fewer visualized glands preoperatively, and preoperative PTH > 2000 pg/mL. Elevated alkaline phosphatase levels (>300 U/L), severe bone pain, and the TPTX procedure itself were significant predictors of HBS. Conclusions: Surgical strategy for SHPT should be individualized, balancing the lower recurrence risk associated with TPTX + AT against its higher likelihood of postoperative hypocalcemia. Preoperative biochemical markers and clinical features could potentially influence operative decision-making and optimize patient outcomes. Full article

Background/Objectives: Primary hyperparathyroidism (PHPT) has been associated with systemic inflammation and metabolic disturbances. This study aimed to evaluate changes in the Systemic Immune-Inflammation Index (SII) and Prognostic Nutritional Index (PNI) following parathyroidectomy (PTX) in PHPT patients, and to assess their return toward healthy control values. Materials and Methods: This retrospective study was conducted between January 2010 and March 2022. It analyzed the demographic characteristics, clinical findings, and laboratory results of patients diagnosed with and operated for PHPT, with comparisons to healthy controls. Postoperative values were recorded at least six months after surgery. Bone mineral density was classified according to World Health Organization criteria, and nephrolithiasis was assessed with imaging. Results: After applying exclusion criteria, 415 PHPT patients and 410 controls were included. PHPT patients were older (p < 0.001) and had a higher proportion of females (p = 0.016). Compared to controls, they had lower phosphorus, albumin, high-density lipoprotein cholesterol, total cholesterol, hemoglobin, and PNI (p < 0.001 for all), while triglycerides, monocytes, platelets, CRP, and SII were higher (p < 0.05). Postoperatively, albumin, platelets, total cholesterol, and triglycerides increased (p < 0.001), while calcium, white blood cell count, neutrophils, lymphocytes, and CRP decreased (p < 0.05), approaching healthy control values. In age- and sex-matched comparisons (propensity score matching, n = 259 in each group), platelets (p = 0.002) and hemoglobin (p = 0.018) were found to be higher postoperatively. Conclusions: Preoperative SII and PNI levels were significantly altered in PHPT patients compared to healthy controls. Following PTX, both of these markers and other parameters showed significant improvements, reflecting positive changes in systemic inflammation and nutritional status. Full article

Background: Several recent studies have documented an increased cardiovascular risk in patients with primary hyperparathyroidism (PHPT), thereby stimulating interest in the association with uric acid (UA), a metabolite linked to cardiovascular disease and chronic kidney disease (CKD) progression, whose role in these conditions is still the subject of study. The aim of this review is to summarize the underlying pathophysiological mechanisms of the PHPT-UA relation and discuss their potential clinical implications. Methods: We conducted a comprehensive literature review, with a focus on the physiological and clinical aspects of the relationship between PHPT and UA. Results: The evidence in the literature supports the association between PHPT and elevated UA levels, although the underlying mechanisms still need to be elucidated. Key mechanisms seem to involve tubular and intestinal transporters, particularly the ABCG2 transporter, as well as indirect effects mediated by hypercalcemia and inflammatory processes. Conclusions: The association between PHPT and UA, though recognized for years, highlights the existence of linked pathophysiological mechanisms between mineral and purine metabolism. However, the current knowledge does not clarify whether uric acid plays an active role in the development of complications related to hyperparathyroidism or if it just represents an indirect marker of metabolic dysfunction. In the absence of specific guidelines, measuring UA levels to screen for hyperuricemia, especially in patients with additional risk factors, should be considered to prevent related complications. Future studies could clarify the role of UA in PHPT, improving our understanding of the disease and potentially leading to new therapeutic strategies to prevent cardiovascular, renal and joint manifestations. Full article

Primary hyperparathyroidism is commonly caused by parathyroid adenomas, hyperplasia, or, rarely, carcinoma. In up to 20% of cases, parathyroid tissue may be ectopic, often located in the mediastinum due to aberrant embryologic migration. Ectopic parathyroid glands pose a diagnostic and therapeutic challenge, and an accurate preoperative localization is essential for an effective and safe resection. Imaging modalities such as CT scan, TC-sestamibi scintigraphy, PET/CT, ultrasonography and MRI are routinely employed, whereas combined techniques offer improved diagnostic accuracy. Emerging approaches, however, including PET/CT with choline tracers, have shown promise in enhancing sensitivity in complex or recurrent cases. When ectopic glands are in the mediastinum, thoracic surgical intervention is required. Traditional open approaches, such as sternotomy or thoracotomy, are associated with significant morbidity. The development and evolution of minimally invasive surgery (MIS) has become the preferred approach in selected cases. When MIS is performed, intraoperative assessment and parathyroid identification are crucial to ensure complete gland removal. Intraoperative parathyroid hormone (ioPTH) monitoring provides real-time confirmation of surgical success. The integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques significantly improves surgical outcomes while minimizing complications and accelerating patient recovery. Ultimately, the effective treatment of ectopic parathyroid glands relies on a personalized approach, adapting both diagnostic and surgical strategies to the unique anatomical and clinical context of each patient. Integration of advanced imaging, intraoperative monitoring, and minimally invasive techniques, combined with a multidisciplinary team involving endocrinologists, radiologists, and thoracic surgeons, is key to optimizing outcomes and reducing patient morbidity. Full article

Background: Vitamin D is a steroid hormone, essential for the immune system and bone health. Since the sun is meant to provide at least 80% of daily vitamin D requirements, the COVID-19 pandemic is likely to have induced a considerable influence on calcium metabolism. Methods: We analyzed data from 1138 children, seen in an outpatient pediatric endocrinology clinic from 2022–2023. Vitamin D status was classified as deficiency if 25(OH)D ≤ 20 ng/mL, insufficiency < 30 ng/mL, and sufficiency ≥ 30 ng/mL. Results: Overall, 60.8% of children had vitamin D deficiency or insufficiency worsened with age (p < 0.005), and with adolescent males having higher 25(OH)D concentrations than females (p < 0.05). A negative correlation was found between 25(OH)D and BMI SDS (R² = 0.02, p < 0.001), and 25(OH)D concentrations varied seasonally, decreasing in winter. Subclinical hyperparathyroidism [parathyroid hormone (PTH) > 45 pg/mL) and normal calcium] was found in 21.5% of children, with 73.5% of them being vitamin D deficient or insufficient. A negative correlation between PTH and 25(OH)D was observed, with PTH plateauing at 25(OH)D above 40 ng/mL (p < 0.001). Conclusions: Compared to the pre-pandemic data (2016–2018), with only 5.1% of children having subclinical hyperparathyroidism (p < 0.001), these findings suggest a marked deterioration in vitamin D status and calcium metabolism in children, with possible unforeseen consequences for bone, immune, and general health. Full article

Background: Patients awaiting total hip arthroplasty (THA), particularly those with hip osteoarthritis (OA), face an elevated risk of osteoporosis due to age and gender-related factors. Osteoporosis, indicated by low bone mineral density (BMD), can affect implant osteointegration, long-term stability, and increase the likelihood of periprosthetic fractures. Despite these risks, osteoporosis is often underdiagnosed and undertreated in THA candidates. While several studies have addressed this issue in Northern populations, data on Southern European cohorts, particularly Italian patients, remain limited. This study aims to evaluate the prevalence of osteoporosis and vitamin D deficiency, as well as the rates of related treatments, in patients with hip osteoarthritis scheduled for THA. Methods: This single-center, retrospective study was conducted at Policlinico Universitario di TorVergata, Italy, involving 66 hip OA patients (35 men, 31 women; mean age 67.5 years). BMD was assessed at the femoral neck, total femur, and lumbar spine via DEXA, alongside vitamin D and PTH levels. Demographic data, ongoing anti-osteoporotic therapies, Harris Hip Score (HHS), and handgrip strength were recorded. Statistical analysis included t-tests and Pearson’s correlation. Osteoporosis was defined per WHO criteria, with significance set at p < 0.05. Results: In this study of 66 patients with hip osteoarthritis (35 men, 31 women; mean age 67.5 years), women exhibited significantly lower bone mineral density (BMD) at the total femur (−0.98 ± 1.42 vs. −0.08 ± 1.04; p < 0.05) and lumbar spine (−0.66 ± 1.74 vs. 0.67 ± 1.59; p < 0.05) compared to men. Handgrip strength was also significantly reduced in females (17.1 ± 8.2 kg) versus males (27.3 ± 10.3 kg; p < 0.05). Vitamin D levels were below 30 ng/mL in 89.4% of patients, and 63.6% had levels below 20 ng/mL; PTH levels were elevated (>65 pg/mL) in 54.5% of cases, indicating frequent secondary hyperparathyroidism. Only 9 patients were receiving vitamin D supplementation and none were on anti-osteoporotic treatment. Conclusions: These findings highlight the frequent coexistence of low BMD, vitamin D deficiency, and reduced muscle strength in THA candidates, suggesting a pattern of musculoskeletal vulnerability that warrants clinical attention. Full article

It is now widely recognized that maintaining magnesium (Mg) homeostasis is critical for health, especially in the context of chronic kidney disease (CKD). Patients with CKD commonly develop hyperphosphatemia and secondary hyperparathyroidism, which are controlled by therapies targeting intestinal phosphate absorption and circulating calcium levels or by modulating parathyroid calcium sensing. Notably, Mg supplementation may provide dual benefits by promoting bone formation and maintaining normal mineralization with slightly elevated serum levels. Importantly, low Mg levels are associated with mortality risk in CKD, highlighting the importance of maintaining adequate serum Mg levels in these patients. Particularly, kidney transplant (KT) patients have lower circulating Mg levels, likely due to interactions with immunosuppressive treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown survival benefits in CKD and increased serum Mg levels, suggesting that Mg regulation may contribute to these outcomes. Overall, Mg plays a key role in CKD-associated mineral and bone disorders (CKD-MBD). Thus, understanding the mechanisms underlying the alteration of Mg homeostasis in CKD could improve clinical outcomes. This review summarizes the basic and clinical studies demonstrating (1) the key actions of Mg in CKD-MBD, including secondary hyperparathyroidism and bone abnormalities; (2) the distinctive profile of KT patients for Mg homeostasis; and (3) the interaction between commonly used drugs, such as SGLT2 inhibitors or immunosuppressive treatments, and Mg metabolism, providing a broad understanding of both the key role of Mg in the context of CKD and the treatments that should be considered to manage Mg levels in CKD patients. Full article

Hypercalcemia is frequently attributed to primary hyperparathyroidism, commonly a result of parathyroid adenomas. Ectopic hyperparathyroidism is characterized by hyperfunctioning parathyroid tissue located outside of expected anatomical locations of endocrine tissue. In this report, we present a rare case of hypercalcemia secondary to a mediastinal ectopic parathyroid adenoma, located between the left atrium and pulmonary artery. Given the unique location of the ectopic gland, diagnosis was delayed with additional complications that followed due to difficulty accessing the gland surgically. Despite this, urgent surgical removal of the ectopic gland allowed for remarkable improvement in presenting symptoms. This clinical case highlights diagnostic and therapeutic challenges that present a unique situation worthy of clinical discussion. Full article

The clinicopathological and molecular features of synchronous parathyroid carcinoma (PC) and thyroid carcinoma in a male patient are presented. At 11, he received mantle field radiotherapy for Hodgkin lymphoma. He had a 26-year adulthood history of recurrent nephrolithiasis treated five times with lithotripsy. At 52, he was referred to our clinic for hypercalcemia. Primary hyperparathyroidism was diagnosed (calcium: 3.46 mmol/L, parathormone: 150 pmol/L, preserved renal function, nephrolithiasis, and osteoporosis). Neck ultrasound revealed a 41 × 31 × 37 mm nodule in the left thyroid and smaller nodules in the right thyroid. Enlarged cervical lymph nodes were not observed. The large nodule was interpreted as parathyroid adenoma on 99Tc-pertechnetate scintigraphy/99Tc-MIBI scintigraphy with SPECT/CT. Total left-sided and subtotal right-sided thyroidectomy were performed. Histopathology confirmed locally invasive, low-grade PC (pT2; positive for parafibromin and E-cadherin, negative for galectin-3 and PGP9.5; wild-type expression for p53 and retinoblastoma protein; Ki-67 index 10%) and incidental papillary thyroid carcinoma (pT1b). Genetic profiling revealed no loss in CDC73, MEN1, CCND1, PIK3CA, CDH1, RB1, and TP53 genes. Deletions in CDKN2A, LATS1, ARID1A, ARID1B, RAD54L, and MUTYH genes and monosomies in nine chromosomes were identified. The tumor mutational burden and genomic instability score were low, and the tumor was microsatellite-stable. The thyroid carcinoma exhibited a TRIM24::BRAF fusion. Following surgery, the parathormone and calcium levels had normalized, and the patient underwent radioiodine treatment for thyroid cancer. The follow-up of 14 months was eventless. In summary, the clinical, laboratory, and imaging features of hyperparathyroidism taken together could have suggested malignancy, then confirmed histologically. The synchronous carcinomas were most likely caused by irradiation treatment diagnosed 41 years after exposure. It seems that the radiation injury initially induced parathyroid adenoma in young adulthood, which underwent a malignant transformation around age fifty. Full article