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Journal of Cellular and Molecular... Apr 2024Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have...
Secondary hyperparathyroidism has a significant impact on the overall well-being of the body. Capsiates, known for their antioxidant and metabolic properties, have emerged as a promising alternative treatment for secondary hyperparathyroidism. This study aims to evaluate the effects and mechanisms of capsiates in the treatment of secondary hyperparathyroidism. To achieve our research objectives, we conducted a study on patients' serum and examined changes in metabolic markers using serum metabolomics. We induced secondary hyperparathyroidism in rat through dietary intervention and divided them into four groups. The first group, referred to as the Parathyroid Hormone (PTH) group, received a low-calcium and high-phosphate diet (0.2% calcium, 1.2% phosphorus). The second group served as the control group, receiving a standard phosphate and calcium diet (0.6% calcium, 0.6% phosphorus). The third group, called the capsiates group, consisted of rat from the control group treated with capsiates (intraperitoneal injection of 2 mg/kg capsiates for 2 weeks after 2 weeks of dietary intervention). The fourth group was the capsiates-treated PTH group. Subsequently, we conducted ribose nucleic acid (RNA) sequencing on parathyroid gland cells and evaluated serum thyroxine levels, oxidative stress, expression of proteins associated with vascular neogenesis, measurement of SOD, GSH and 3-nitrotyrosine, micro-CT and histological staining. The serum metabolomic data revealed a significant decrease in capsiate levels in the secondary hyperparathyroidism group. Administration of capsiates to PTH rat resulted in increased calcium levels compared to the PTH group. Additionally, the PTH + Capsiates group showed significantly lower levels of PTH and phosphate compared to the PTH group. The PTH group exhibited a notable increase in the quantity and size of mitochondria compared to the control group. Following capsiates administration to the PTH group, there was a significant reduction in the number of mitochondria and length of microvilli, but an increase in the size of mitochondria compared to the PTH group. Sequencing analysis revealed that vascular endothelial growth factor (VEGF) and Vascular Endothelial Growth Factor Receptor 1 (VEGFR1) play crucial roles in this process. Vascular-related variables and downstream signalling were significantly elevated in hyperthyroidism and were alleviated with capsaicin treatment. Finally, combining capsiates with the PTH group improved bone mineral density, Tb.N, BV.TV, Cs.Th, Tt.Ar, OPG, Ob.TV and Oc.TV, as well as the mineral apposition rate, but significantly decreased Tb.Sp and Receptor Activator for Nuclear Factor-κ B Ligand (RANKL) compared to the PTH group. The findings suggest that capsiates can improve secondary hyperparathyroidism and ameliorated osteoporosis outcomes by inhibiting angiogenesis and reducing oxidative stress.
Topics: Humans; Rats; Animals; Calcium; Capsaicin; Angiogenesis; Insulin Resistance; Vascular Endothelial Growth Factor A; Hyperparathyroidism, Secondary; Parathyroid Hormone; Phosphorus; Phosphates
PubMed: 38591872
DOI: 10.1111/jcmm.18202 -
Jornal Brasileiro de Nefrologia 2024Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L)...
INTRODUCTION
Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients.
METHODS
A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed.
RESULTS
There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count.
CONCLUSION
N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.
Topics: Humans; Parathyroidectomy; Renal Dialysis; Parathyroid Hormone; Neutrophils; Renal Insufficiency, Chronic; Hyperparathyroidism, Secondary; Calcium; Biomarkers; Inflammation; Lymphocytes
PubMed: 38591824
DOI: 10.1590/2175-8239-JBN-2023-0175en -
Molecular Genetics & Genomic Medicine Apr 2024Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare inherited disorder characterized by proportionate short stature, skeletal defects, ocular and dental... (Review)
Review
BACKGROUND
Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare inherited disorder characterized by proportionate short stature, skeletal defects, ocular and dental abnormalities, and transient hypocalcemia. It is caused by variants in FAM111A gene. Diagnosis of KCS2 can be challenging because of its similarities to other syndromes, the absence of clear hallmarks and the deficient number of genetically confirmed cases. Here, we aimed to further delineate and summarize the genotype and phenotype of KCS2, in order to get a better understanding of this rare disorder, and promote early diagnosis and intervention.
METHODS
We present clinical and genetic characteristics of eight newly affected individuals with KCS2 from six families, including one family with three individuals found to be a father-to-daughter transmission, adding to the limited literature. Furthermore, we performed a review of genetically confirmed KCS2 cases in PubMed, MEDLINE and CNKI databases.
RESULTS
There were six females and two males in our cohort. All the patients presented with short stature (100.0%). Clinical manifestations included ocular defects such as hypermetropia (5/8), dental problems such as defective dentition (3/8) and dental caries (3/8), skeletal and brain anomalies such as delayed closure of anterior fontanelle (6/8), cerebral calcification (3/8), cortical thickening (3/8) and medullary stenosis (4/8) of tubular bones. Endocrinologic abnormalities included hypoparathyroidism (5/8) and hypocalcemia (3/8). One male patient had micropenis and microorchidism. All cases harboured missense variants of FAM111A, and nucleotides c.1706 arose as a mutational hotspot, with seven individuals harbouring a c.1706G>A (p.Arg569His) variant, and one child harbouring a c.1531T>C (p.Tyr511His) variant. Literature review yielded a total of 46 patients from 20 papers. Data analysis showed that short stature, hypoparathyroidism and hypocalcemia, ocular and dental defects, skeletal features including cortical thickening and medullary stenosis of tubular bones, and seizures/spasms were present in more than 70% of the reported KCS2 cases.
CONCLUSION
We provide detailed characteristics of the largest KCS2 group in China and present the first genetically confirmed instance of father-to-daughter transmission of KCS2. Our study confirms that Arg569His is the hot spot variant and summarizes the typical phenotypes of KCS2, which would help early diagnosis and intervention.
Topics: Child; Female; Humans; Male; Hypocalcemia; Constriction, Pathologic; Dental Caries; Phenotype; Genotype; Hypoparathyroidism; Dwarfism; Hyperostosis, Cortical, Congenital
PubMed: 38591167
DOI: 10.1002/mgg3.2433 -
Cureus Mar 2024Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations in the tumor suppressor gene and is characterized by parathyroid,...
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder caused by mutations in the tumor suppressor gene and is characterized by parathyroid, pancreatic islet, and anterior pituitary tumors. Primary hyperparathyroidism is the most characteristic finding in MEN1, and intraoperative identification and accurate removal of the diseased parathyroid glands are vital since incomplete excision results in recurrence. This case report describes a 59-year-old woman who had pancreatic islet cell tumors and pituitary tumors and underwent selective transsphenoidal adenomectomy. Based on her medical history and examination, the diagnosis of primary hyperparathyroidism in MEN1 was made, and she underwent total parathyroidectomy with autotransplantation with SPY-Elite®️ Fluorescence Imaging (Stryker Corp., Kalamazoo, MI). Intraoperative identification of the parathyroid glands using autofluorescence with real-time intrinsic near-infrared (NIR) imaging made it easier to detect all of the parathyroid hyperplasia. After the surgery, she had hypoparathyroidism and continued with her oral calcium and vitamin D supplementation to maintain normal calcium levels during follow-up. Herein, we would like to advocate that the use of parathyroid gland autofluorescence with real-time intrinsic NIR imaging may be useful for identifying parathyroid tumors in patients with primary hyperparathyroidism in MEN1.
PubMed: 38586714
DOI: 10.7759/cureus.55706 -
Cureus Mar 2024Neck lumps can be a symptom of thyroid and parathyroid gland metabolic diseases, and papillary thyroid carcinoma is reported in some cases. It is commonly observed in...
Neck lumps can be a symptom of thyroid and parathyroid gland metabolic diseases, and papillary thyroid carcinoma is reported in some cases. It is commonly observed in middle-aged people with a female predominance. Papillary carcinoma of the thyroid is the most common type of thyroid cancer, originating from the thyroid gland cells. It is slow-growing and less aggressive, but it has been reported to have the ability to affect nearby lymph nodes and other organs. It is associated with the RET protooncogene, NTRK1, and MET genes. Early detection is crucial, especially for middle-aged patients. Treatment typically involves thyroidectomy and radioactive iodine therapy, with the need for hormone replacement therapy. Fine-needle aspiration cytology (FNAC) is an efficient and cost-effective tool for diagnosing neck swellings, leading to a conclusive diagnosis of the mass. We present a case of a 60-year-old Indian female with swelling over the neck for the past six years, which was recently accompanied by dyspnea, hand tremors, and palpitations. The ignored neck mass was found to be a hyper-echoic mass with macro calcifications and cystic degeneration on ultrasonography, confirmed as papillary thyroid carcinoma by FNAC, followed by a complete thyroidectomy and uneventful follow-up.
PubMed: 38586692
DOI: 10.7759/cureus.55627 -
Genetics Research 202422q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes,...
22q11.2 deletion syndrome (22q11.2DS) is a microdeletion syndrome with a broad and heterogeneous phenotype, even though most of the deletions present similar sizes, involving ∼3 Mb of DNA. In a relatively large population of a Brazilian 22q11.2DS cohort (60 patients), we investigated genetic variants that could act as genetic modifiers and contribute to the phenotypic heterogeneity, using a targeted NGS (Next Generation Sequencing) with a specific Ion AmpliSeq panel to sequence nine candidate genes (, , , , , , , , and ), mapped in and outside the 22q11.2 hemizygous deleted region. prediction was performed, and the whole-genome sequencing annotation analysis package (WGSA) was used to predict the possible pathogenic effect of single nucleotide variants (SNVs). For the prediction of the indels, we used the genomic variants filtered by a deep learning model in NGS (GARFIELD-NGS). We identified six variants, 4 SNVs and 2 indels, in , , and genes with possibly synergistic deleterious effects in the context of the 22q11.2 deletion. Our results provide the opportunity for the discovery of the co-occurrence of genetic variants with 22q11.2 deletions, which may influence the patients´ phenotype.
Topics: Humans; DiGeorge Syndrome; Phenotype; Brazil; Chromosome Deletion
PubMed: 38586596
DOI: 10.1155/2024/5549592 -
Frontiers in Endocrinology 2024The disorders in the metabolism of calcium can present with manifestations that strongly suggest their diagnosis; however, most of the time, the symptoms with which they...
INTRODUCTION
The disorders in the metabolism of calcium can present with manifestations that strongly suggest their diagnosis; however, most of the time, the symptoms with which they are expressed are nonspecific or present only as a laboratory finding, usually hypercalcemia. Because many of these disorders have a genetic etiology, in the present study, we sequenced a selection of 55 genes encoding the principal proteins involved in the regulation of calcium metabolism.
METHODS
A cohort of 79 patients with hypercalcemia were analyzed by next-generation sequencing.
RESULTS
The 30% of our cohort presented one pathogenic or likely pathogenic variant in genes associated with hypercalcemia. We confirmed the clinical diagnosis of 17 patients with hypocalciuric hypercalcemia (pathogenic or likely pathogenic variants in the and genes), one patient with neonatal hyperparathyroidism (homozygous pathogenic variant in the gene), and another patient with infantile hypercalcemia (two pathogenic variants in compound heterozygous state in the gene). However, we also found variants in genes associated with primary hyperparathyroidism (), renal hypophosphatemia with or without rickets (, , , , and ), DiGeorge syndrome ( and ), and hypophosphatasia (). Our genetic study revealed 11 novel variants.
CONCLUSIONS
Our study demonstrates the importance of genetic analysis through massive sequencing to obtain a clinical diagnosis of certainty. The identification of patients with a genetic cause is important for the appropriate treatment and identification of family members at risk of the disease.
Topics: Infant, Newborn; Humans; Hypercalcemia; Calcium; Genetic Profile; Mutation; Hyperparathyroidism
PubMed: 38586466
DOI: 10.3389/fendo.2024.1297614 -
Archives of Endocrinology and Metabolism Apr 2024This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation andcardiovascular...
OBJECTIVE
This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation andcardiovascular risk calculators.
SUBJECTS AND METHODS
Patients with post-surgical hypoparathyroidism (HG = 29) were compared to a control group (CG = 29), matched by sex and age. Demographic and clinical data were captured by a questionnaire or patient files. Both groups performed a thoracic-computed tomography to evaluate the CACS and the cardiovascular risk was calculated by two risk calculators.
RESULTS
In the HG, the supplementation of calcium varied between 500 to 2,000 mg/day and the mean calcitriol was 0.5 ± 0.29 mcg/day. The mean serum calcium and phosphorus were 8.32 ± 0.68 and 4.92 ± 0.87 mg/dL, respectively, and in the range recommended for hypoparathyroidism. The Brazilian Society of Cardiology's risk calculator showed a difference among groups, with no patient in the HG with low risk, but the CACS was similar. A positive CACS in the HG was associated with obesity and high BMI but not with calcium and/or vitamin D supplementation.
CONCLUSION
In conclusion, patients with hypoparathyroidism did not show increased CACS, and it was not related to supplementation.
Topics: Humans; Calcium; Hypoparathyroidism; Brazil; Coronary Artery Disease
PubMed: 38578437
DOI: 10.20945/2359-4292-2023-0053 -
Cancer Reports (Hoboken, N.J.) Apr 2024Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal...
BACKGROUND
Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia.
CASE
A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range.
CONCLUSION
The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.
Topics: Male; Humans; Middle Aged; Hypocalcemia; Parathyroid Neoplasms; Calcium; Hypercalcemia; Fractures, Spontaneous; Phosphorus; Muscular Atrophy; Pain
PubMed: 38577726
DOI: 10.1002/cnr2.2047 -
Journal of Cardiothoracic Surgery Apr 2024Hyperparathyroidism (HPT) is a disease caused by hypersecretion of one or more parathyroid glands, it can be associated with ectopic mediastinal parathyroid glands... (Review)
Review
BACKGROUND
Hyperparathyroidism (HPT) is a disease caused by hypersecretion of one or more parathyroid glands, it can be associated with ectopic mediastinal parathyroid glands (MEPA) in 2% of cases. The use of video-assisted thoracoscopic surgery (VATS) for the surgical resection of these glands is a safe, cost-effective, and low morbidity option for patients with MEPA. We report a case series of patients with this disease managed with VATS, the first in Mexico and Latinamerica.
METHODS
From 2008 to 2022, a retrospective study involving patients with MEPA and treated by VATS approach was performed in a tertiary hospital in Mexico city. Relevant biochemical and clinical variables such as imaging studies, pre and postoperative laboratory results, surgical strategy, outcomes and pathological analysis were analyzed.
RESULTS
Four cases of mediastinal parathyroid adenomas causing HPT were included. All patients were female with a median age of 52.5 years-old (range 46-59 years), half of the patients had primary HPT and the others tertiary HPT after kidney transplant. 75% of cases had a MEPA in the medium mediastinum, all had a preoperative positive SPECT-CT 99mTc Sestamibi scan. Mean preoperative PTH was 621.3pg/mL (182-1382pg/mL). All patients successfully underwent parathyroidectomy with a VATS approach, no deaths were reported.
CONCLUSIONS
VATS is a minimally invasive surgery that provides adequate access to mediastinal located glands, optimal visualization of mediastinal structures and has a high resection success rate with less complications and morbidity than open approaches.
Topics: Humans; Female; Middle Aged; Male; Parathyroid Neoplasms; Mediastinum; Retrospective Studies; Parathyroid Glands; Parathyroidectomy; Technetium Tc 99m Sestamibi
PubMed: 38575949
DOI: 10.1186/s13019-024-02694-y