Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are often complicated by high-turnover renal osteodystrophy (HTRO) and secondary hyperparathyroidism (SHPT), characterized by disturbances in mineral metabolism and skeletal abnormalities. Genetic variations within the vitamin D receptor (VDR) gene, known as VDR gene polymorphisms, have been implicated in modulating the susceptibility to HTRO and SHPT. This systematic review aims to evaluate the existing literature on the association between VDR gene polymorphisms and the development of these complications in ESRD and hemodialysis patients. A comprehensive literature search across multiple databases was conducted, and studies investigating VDR gene polymorphisms and HTRO or SHPT in ESRD or hemodialysis patients were included. The included studies examined various VDR gene polymorphisms, such as BsmI, ApaI, TaqI, and FokI, and their associations with clinical outcomes like parathyroid hormone (PTH) levels, bone mineral density, and the development of SHPT or HTRO. The findings suggest that certain VDR gene polymorphisms, notably the ApaI \"aa\" genotype, BsmI \"bb\" genotype, TaqI \"tt\" genotype, and FokI variant, may contribute to the pathogenesis of SHPT and HTRO by affecting PTH levels, bone turnover markers, and vitamin D sensitivity. However, the studies had relatively small sample sizes and were conducted in different populations, limiting generalizability. Further larger-scale studies, functional investigations, and exploration of gene-environment interactions are warranted to elucidate the underlying mechanisms and facilitate personalized treatment approaches for CKD and ESRD patients with mineral and bone disorders.

OBJECTIVE: The management of primary hyperparathyroidism (PHPT) during pregnancy may be surgical or conservative. This study compared adverse outcomes between surgical and non-surgical treatments. Additionally, the study investigated the correlation between serum calcium values and complication rates.
METHODS: A systematic review of retrospective studies, case series, and case reports. Biochemical parameters, interventions, and outcomes of each pregnancy were recorded. The study population comprised two groups: the non-surgical and surgical groups. Adverse outcomes were categorized as maternal, obstetric, or neonatal.
RESULTS: The surgical and non-surgical groups consisted of 163 and 185 patients, respectively. A positive correlation was observed between the mean maternal gestational calcium value and both maternal and obstetric complication. Neonatal complications were more prevalent in patients treated conservatively across all maternal calcium values (p < 0.001). No significant differences were observed in maternal outcomes and overall obstetric outcomes between the study groups, albeit a higher mean serum calcium value in the surgical group (12.3 mg/dL) compared with the non-surgical group (11.1 mg/dL).
CONCLUSIONS: Given the significantly lower neonatal adverse outcomes in the surgical group compared to the non-surgical group, along with non-inferior maternal and obstetric outcomes in the surgical group, the overall data of this study suggest that parathyroidectomy is favorable to non-surgical management even in cases of mild hypercalcemia.

Phosphate is freely filtered by the glomerulus and reabsorbed exclusively in the proximal tubule by two key transporters, NaPiIIA and NaPiIIC, encoded by SLC34A1 and SLC34A3, respectively. Regulation of these transporters occurs primarily through the hormone FGF23 and, to a lesser degree, PTH. Consequently, inherited non-FGF23 mediated phosphaturic disorders are due to generalised proximal tubular dysfunction, loss-of-function variants in SLC34A1 or SLC34A3 or excess PTH signalling. The corresponding disorders are Renal Fanconi Syndrome, Infantile Hypercalcaemia type 2, Hereditary Hypophosphataemic Rickets with Hypercalciuria and Familial Hyperparathyroidism. Several inherited forms of Fanconi renotubular syndrome (FRTS) have also been described with the underlying genes encoding for GATM, EHHADH, HNF4A and NDUFAF6. Here, we will review their pathophysiology, clinical manifestations and the implications for treatment from a kidney-centric perspective, focussing on those disorders caused by dysfunction of renal phosphate transporters. Moreover, we will highlight specific genetic aspects, as the availability of large population genetic databases has raised doubts about some of the originally proposed gene-disease associations concerning phosphate transporters or their associated proteins.

BACKGROUND: As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion\'s location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas.
METHODS: We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient\'s symptoms disappeared and serum levels of PTH and calcium normalized.
CONCLUSIONS: SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

UNASSIGNED: Primary hyperparathyroidism (PHPT) is the underlying etiology for 90% of patients with hypercalcemia. PHPT patients have traditionally been characterized as being symptomatic or asymptomatic. However, we submit that even \"asymptomatic\" patients may still have clinical features, posing the idea of coining asymptomatic disease as a misnomer. This paper presents a systematic review and meta-analysis elucidating the differences between asymptomatic and symptomatic PHPT in the literature.
UNASSIGNED: A comprehensive literature search was conducted in PubMed, Cochrane, and Web of Science databases for articles published from 2012 to 2022. Inclusion criteria consisted of all studies comparing symptomatic and asymptomatic PHPT patients. Two reviewers independently evaluated the literature using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The level of evidence was determined using the Oxford Center for Level of Evidence-Based Medicine. Data were extracted, and a meta-analysis was performed. I2 index was employed for heterogeneity.
UNASSIGNED: There were 18 studies included, with a total of 4238 patients. The average age of patients included was 56.37, with 25.7% of the cohort being male. Several studies reported clinical features even for the \"asymptomatic\" group. Patients in the symptomatic group tended to have higher levels of PTH and calcium. The asymptomatic group had greater levels of vitamin D. There was observed heterogeneity between the studies.
UNASSIGNED: More extreme PTH, calcium values, and low vitamin D levels were seen in patients with symptomatic disease. However, asymptomatic patients occasionally exhibited clinical features. Therefore, the terminology of \"asymptomatic\" disease is likely inappropriate for these patients.

Osteoporosis is a common disease, defined primarily by a low measured bone density, which is associated with an increased risk of fragility fractures. Low calcium intake and vitamin D deficiency seem to be positively correlated with the prevalence of osteoporosis. Although they are not suitable for the diagnosis of osteoporosis, the biochemical markers of bone turnover can be measured in serum and/or urine, enabling the assessment of the dynamic bone activity and the short-term effectiveness of the osteoporosis treatment. Calcium and vitamin D are essential for maintaining bone health. The aim of this narrative review is to summarize the effects of vitamin D and calcium supplementation separately and in combination, on bone density and circulating serum and blood plasma vitamin D, calcium, parathyroid hormone levels, markers of bone metabolism concentrations, and clinical outcomes, such as falls and osteoporotic fractures. We searched the PubMed online database to find clinical trials from the last five years (2016-April 2022). A total of 26 randomized clinical trials (RCTs) were included in this review. The present reviewed evidence suggests that vitamin D alone or in combination with calcium increases circulating 25(OH)D. Calcium with concomitant vitamin D supplementation, but not vitamin D alone, leads to an increase in BMD. In addition, most studies did not detect significant changes in circulating levels of plasma bone metabolism markers, nor in the incidence of falls. Instead, there was a decrease in blood serum PTH levels in the groups receiving vitamin D and/or Ca supplementation. The plasma vitamin D levels at the beginning of the intervention, and the dosing regimen followed, may play a role in the observed parameters. However, further study is needed to determine an appropriate dosing regimen for the treatment of osteoporosis and the role of bone metabolism markers.

BACKGROUND: Neuroendocrine neoplasms (NEN) originate from neuroendocrine cells ubiquitously spread throughout the body. Hypercalcemia associated with cancer is the most common life-threatening metabolic disorder in patients with advanced stage cancer. Paraneoplastic hypercalcemia is more commonly associated with hematological malignancies, renal and breast carcinomas, and squamous cell carcinomas, but it has also been described in patients with well-differentiated NEN, where it often remains undiagnosed. Among its causes, systemic secretion of parathyroid hormone-related protein (PTHrP) and ectopic production of 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) may be considered paraneoplastic causes of hypercalcemia. In order to clarify the diagnostic work up of paraneoplastic hypercalcemia in patients with NEN, we perform a systematic review, which is lacking in the literature.
METHODS: We performed a data search using MEDLINE and SCOPUS including papers from 1961 to 2021. We selected articles on paraneoplastic hypercalcemia associated with well-differentiated NEN.
RESULTS: The search led to the selection of 78 publications for a total of 114 patients. Pooled data showed that the most frequent primary tumor site associated with paraneoplastic hypercalcemia was pancreatic NEN, followed by Pheochromocytoma. In most cases, paraneoplastic hypercalcemia was caused by PTHrP production and secretion. In more than two thirds of cases, paraneoplastic hypercalcemia was present at the time of NEN diagnosis and, in metachronous cases, was related to local recurrence, distant metastasis development, or tumor progression. In most patients, a combination of therapeutic approaches was employed, and reduction of the tumor burden was essential to control the paraneoplastic syndrome.
CONCLUSIONS: The onset of hypercalcemia associated with cancer in patients with well-differentiated NEN represents a major clinical challenge. The complex clinical and therapeutical management of paraneoplastic hypercalcemia implies the need for a multidisciplinary approach, aimed at controlling the clinical syndrome and tumor growth.

Currently, there is no consensus on the optimal vitamin D administration in bariatric patients. The present systematic review and meta-analysis were conducted to examine the effect of vitamin D supplements on serum level of 25(OH) vitamin D in the patients undergoing bariatric surgery (BS).Random model effects were used to estimate standardized mean difference (SMD) with a 95% confidence interval (CI). Nine clinical trials were included in the meta-analysis. Vitamin D supplementation in patients undergoing BS modestly improves vitamin D status (SMD, 0.53; 95% CI, 0.28, 0.77) particularly, in the dosages above 2850 IU/day and in the patients with BMI greater than 50 kg/m2. Vitamin D supplementation was associated with prevention of raising of the PTH serum concentration and without impact on serum calcium levels.

Parathyroid carcinoma (PC) is a rare malignancy, the incidence of which is less than 1/1 million per year. Sarcomatoid parathyroid carcinoma (SaPC) is an extremely peculiar subtype; only three cases have been reported internationally. It consists of both malignant epithelial components and sarcomatoid components (mesenchymal origin) simultaneously. This \"confusing\" cancer exhibits higher invasiveness, and traditional surgery does not appear to achieve the expectation, which differs significantly from that of general PC.
To characterize the clinicopathologic features of SaPC and explore similarities and differences between SaPC and general PC.
We collected clinical data of SaPC cases from our center and literature. The SaPC case in our center was presented. To better understand the characteristics of SaPC, we also reviewed clinical information in general PC cases from our center and literature within the last 5 years, and a systematic review was performed for further comparison.
A 60-year-old woman was admitted for a neck mass and hoarseness. After the surgery, she was confirmed as SaPC and ultimately developed local recurrence at 3 months. Together with the reported cases from literature, four cases of SaPC (three cases from literature) and 203 cases of general PC (200 cases from literature) were reviewed. Both tumors showed obvious abnormalities in parathormone (PTH) level and gland size. Compared to general PC, SaPC has a later age of onset (60.50 ± 7.42 vs. 51.50 ± 8.29), relatively low levels of PTH (110.28 ± 59.32 vs. 1,156.07 ± 858.18), and a larger tumor size (6.00 ± 1.63 vs. 3.14 ± 0.70). For SaPC, all four cases were initially misdiagnosed as thyroid tumors (4/4). Spindle cell areas or transitional zones were common pathological features in SaPC cases (3/4).
SaPC is a very rare pathologic subtype of PC and appears to be much more easily misdiagnosed as a thyroid tumor. Spindle cell areas or transitional zones are highly possible to be pathological features in its sarcomatoid components. Despite many similarities, there are some differences between SaPC and general PC-SaPC does not show the obvious endocrine feature but stronger aggressiveness. Surgical treatment of SaPC does relieve life-threatening symptoms and improve quality of life even with recurrence in the short term.

Nowadays, chronic kidney disease (CKD) and osteoporosis have become crucial health-related issues globally. CKD-induced osteoporosis is a systemic disease characterized by the disruption of mineral, hormone, and vitamin homeostasis that elevates the likelihood of fracture. Here, we review recent studies on the association of CKD and osteoporosis. In particular, we focus on the pathogenesis of CKD-associated osteoporosis, including the homeostasis and pathways of several components such as parathyroid hormone, calcium, phosphate, vitamin D, fibroblast growth factor, and klotho, as well as abnormal bone mineralization, remodeling, and turnover. In addition, we explore the diagnostic tools and possible therapeutic approaches for the management and prevention of CKD-associated osteoporosis. Patients with CKD show higher osteoporosis prevalence, greater fracture rate, increased morbidity and mortality, and an elevated occurrence of hip fracture. We also rule out that increased severity of CKD is related to a more severe condition of osteoporosis. Furthermore, supplements such as calcium and vitamin D as well as lifestyle modifications such as exercise and cessation of smoking and alcohol help in fracture prevention. However, new approaches and advancements in treatment are needed to reduce the fracture risk in patients with CKD. Therefore, further collaborative multidisciplinary research is needed in this regard.