RESUMEN
Hyperparathyroidism is a common endocrine disorder that occurs secondary to abnormal parathyroid gland functioning. Depending on the type of hyperparathyroidism, surgical extirpation of hyperfunctioning parathyroid glands can be considered for disease cure. Intraoperative parathyroid hormone (IOPTH) monitoring improves outcomes in patients undergoing surgery for primary hyperparathyroidism, but studies are needed to characterize its institutional adoption and its role in surgery for secondary and tertiary hyperparathyroidism, as these entities can be difficult to cure. Hence, we will perform a cross-sectional survey study of surgeon rationale, operational details, and barriers associated with IOPTH monitoring adoption across North America. We will utilize a convenience sampling technique to distribute an online survey to head and neck surgeons and endocrine surgeons across North America. This survey will be distributed via email to three North American professional societies (i.e., Canadian Society for Otolaryngologists-Head and Neck Surgeons, American Head and Neck Society, and American Association of Endocrine Surgeons). The survey will consist of 30 multiple choice questions that are divided into three concepts: (1) participant demographics and training details, (2) details of surgical adjuncts during parathyroidectomy, and (3) barriers to adoption of IOPTH. Descriptive analyses and multiple logistic regression will be used to evaluate the impact of demographic, institutional, and training variables on the use of IOPTH monitoring in surgery for all types of hyperparathyroidism and barriers to IOPTH monitoring adoption. Ethics approval was obtained by the Hamilton Integrated Research Ethics Board (2024-17173-GRA). These findings will characterize surgeon and institutional practices with regards to IOPTH monitoring during parathyroid surgery and will inform future trials aimed to optimize the use of IOPTH monitoring in secondary and tertiary hyperparathyroidism.
Asunto(s)
Monitoreo Intraoperatorio , Hormona Paratiroidea , Paratiroidectomía , Cirujanos , Humanos , Paratiroidectomía/métodos , Hormona Paratiroidea/sangre , Estudios Transversales , Monitoreo Intraoperatorio/métodos , América del Norte , Encuestas y Cuestionarios , Hiperparatiroidismo/cirugíaRESUMEN
ABSTRACT: 99m Tc-MIBI scintigraphy is a nuclear medicine imaging modality commonly used for the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism. In addition, 99m Tc-MIBI can also be used for imaging various tumors due to its unique mechanism of intracellular accumulation. Here, we introduced a case of a single 99m Tc-MIBI SPECT/CT simultaneously visualized two different malignant tumors, such as papillary thyroid cancer and small cell lung cancer, along with a parathyroid adenoma in a patient with hyperparathyroidism. The clinical usefulness of 99m Tc-MIBI SPECT/CT was also explored by comparing it with 18 F-FDG PET/CT among the three tumors.
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Fluorodesoxiglucosa F18 , Hiperparatiroidismo , Neoplasias Pulmonares , Neoplasias de las Paratiroides , Tomografía Computarizada por Tomografía de Emisión de Positrones , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Carcinoma Pulmonar de Células Pequeñas , Tecnecio Tc 99m Sestamibi , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Humanos , Neoplasias de las Paratiroides/diagnóstico por imagen , Neoplasias de las Paratiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/complicaciones , Carcinoma Pulmonar de Células Pequeñas/diagnóstico por imagen , Carcinoma Pulmonar de Células Pequeñas/complicaciones , Cáncer Papilar Tiroideo/diagnóstico por imagen , Cáncer Papilar Tiroideo/complicaciones , Hiperparatiroidismo/diagnóstico por imagen , Carcinoma Papilar/diagnóstico por imagen , Adenoma/diagnóstico por imagen , Adenoma/complicaciones , Persona de Mediana Edad , Femenino , MasculinoRESUMEN
Tertiary hyperparathyroidism (THPT) is characterized by elevated parathyroid hormone and serum calcium levels after kidney transplantation (KTx). To ascertain whether pre-transplant calcimimetic use and dose information would improve THPT prediction accuracy, this retrospective cohort study evaluated patients who underwent KTx between 2010 and 2022. The primary outcome was the development of clinically relevant THPT. Logistic regression analysis was used to evaluate pre-transplant calcimimetic use as a determinant of THPT development. Participants were categorized into four groups according to calcimimetic dose, developing two THPT prediction models (with or without calcimimetic information). Continuous net reclassification improvement (CNRI) and integrated discrimination improvement (IDI) were calculated to assess ability to reclassify the degree of THPT risk by adding pre-transplant calcimimetic information. Of the 554 patients, 87 (15.7%) developed THPT, whereas 139 (25.1%) received pre-transplant calcimimetic treatment. Multivariate logistic regression analysis revealed that pre-transplant calcimimetic use was significantly associated with THPT development. Pre-transplant calcimimetic information significantly improved the predicted probability accuracy of THPT (CNRI and IDI were 0.91 [p < 0.001], and 0.09 [p < 0.001], respectively). The THPT prediction model including pre-transplant calcimimetic information as a predictive factor can contribute to the prevention and early treatment of THPT in the era of calcimimetics.
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Calcimiméticos , Calcio , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Calcimiméticos/uso terapéutico , Calcimiméticos/administración & dosificación , Adulto , Calcio/sangre , Hiperparatiroidismo/tratamiento farmacológico , Hiperparatiroidismo/etiología , Hormona Paratiroidea/sangre , Modelos LogísticosRESUMEN
INTRODUCTION: Brown tumors are reactive osteolytic lesions caused by hyperparathyroidism. These rare lesions are non-neoplastic processes that result from bone resorption. The purpose of this study was to retrospectively review a 34-year experience with brown tumors in our institution. MATERIALS AND METHODS: We retrospectively analyzed the records of 26 consecutive patients with brown tumor who were treated in our institution between May 1988 and October 2020, with a mean follow-up of 36,1 months. RESULTS: 17 male (65,4%) and 9 female (34,6%) patients with a mean age of 41,6 were included in the study. Localized bone pain was present in 13 cases (50,0%) as the first presenting symptom. 3 patients (11,5%) presented with diffuse bone pain. 7 patients (26,9%) were diagnosed with brown tumor while being investigated for pathological fractures. The other 3 patients (11,5%) were diagnosed while being evaluated for hypercalcemia symptoms. 7 patients (26,9%) had solitary lesions, while 19 patients (73,1%) had multiple lesions. Pelvis, femur, ribs, tibia, proximal humerus and mandible were the most common sites of localization. 23 patients (88,5%) were diagnosed with primary hyperparathyroidism, while the other 3 patients (11,5%) had secondary hyperparathyroidism. A total of the 65 lesions, 23 (35.4%) underwent orthopedic surgery, and 42 (64.6%) were followed up conservatively after parathyroidectomy. Orthopedic surgery was performed in 21 of 26 patients, the other 5 cases were followed up conservatively. Intralesional curettage was performed in 19 cases (82,6%). The resulting cavity was filled with bone cement in 11 cases (47,8%). Bone grafting was applied in 8 cases (34,8%). No recurrence was observed in any of the patients. CONCLUSION: The diagnosis of brown tumor begins with clinical suspicion. Endocrinology and general surgery consultation is important before surgery. Treatment of brown tumors requires a multidisciplinary approach.
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Hiperparatiroidismo , Humanos , Masculino , Estudios Retrospectivos , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Anciano , Adolescente , Hiperparatiroidismo/cirugía , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/etiología , Osteítis Fibrosa Quística/etiologíaRESUMEN
Background: Encapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls. Methods: Linear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients. Results: EPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively. Conclusion: High levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.
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Calcinosis , Hiperparatiroidismo , Fibrosis Peritoneal , Humanos , Fibrosis Peritoneal/etiología , Calcio , Factores de Riesgo , Calcinosis/etiología , Minerales , FosfatosRESUMEN
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 CASR and AP2S1 genes), one patient with neonatal hyperparathyroidism (homozygous pathogenic variant in the CASR gene), and another patient with infantile hypercalcemia (two pathogenic variants in compound heterozygous state in the CYP24A1 gene). However, we also found variants in genes associated with primary hyperparathyroidism (GCM2), renal hypophosphatemia with or without rickets (SLC34A1, SLC34A3, SLC9A3R1, VDR, and CYP27B1), DiGeorge syndrome (TBX1 and NEBL), and hypophosphatasia (ALPL). 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.
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Hipercalcemia , Hiperparatiroidismo , Recién Nacido , Humanos , Hipercalcemia/genética , Hipercalcemia/diagnóstico , Calcio , Perfil Genético , Mutación , Hiperparatiroidismo/genéticaRESUMEN
BACKGROUND Secondary hyperparathyroidism and coronary calcifications are common complications in chronic kidney disease. However, the relation between coronary calcium score (CCS) and persistent hyperparathyroidism (pHPT) after kidney transplantation (KT) remains unknown. MATERIAL AND METHODS This was a single-center retrospective study of KT candidates from January 2017 to May 2020. We collected patients' demographics, cardiovascular (CV) risk factors, and the findings of pre-KT CV imaging. We also collected parathyroid hormone (PTH) values before KT, at 1-6 months, 6-12 months, and 12-24 months after KT. We defined pHPT as PTH ≥25.5 pmol/L after 12 months post-KT. RESULTS A total of 111 KT recipients (KTRs) with a mean age of 50.4 years were included, of which 62.2% were men and 77.5% were living-donor KTRs. Dialysis modality used before KT was peritoneal dialysis in 9.9% and hemodialysis in 82.9%. Dialysis vintage was 3±2.9 years. The prevalence of pHPT was 24.3% (n=27), and the prevalence of severe coronary calcifications (CCS >400 Agatston units) was 19.8% (n=22). PTH values at baseline, 1-6 months, 6-12 months, and 12-24 months were not different among between CCS >400 or CCS <400 groups. However, pHPT after KT was significantly more prevalent in KTRs with severe CCS (37% vs 14.3%, p=0.014). Severe CCS was associated with less improvement of PTH values after KT (r=0.288, p=0.020). Otherwise, the findings of cardiac PET and coronary angiogram were not significantly different between pHPT and non-pHPT patients. CCS >400 was independently associated with pHPT after transplant (aOR=18.8, P=0.012). CONCLUSIONS Severe CCS on pre-KT cardiac assessment is associated with pHPT after KT.
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Hiperparatiroidismo , Trasplante de Riñón , Masculino , Humanos , Persona de Mediana Edad , Femenino , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Calcio , Hiperparatiroidismo/complicaciones , Hiperparatiroidismo/epidemiología , Hormona Paratiroidea , Tomografía de Emisión de PositronesRESUMEN
Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.
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Hiperparatiroidismo Secundario , Hiperparatiroidismo , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Paratiroidectomía/efectos adversos , Estudios Retrospectivos , Hiperparatiroidismo/etiología , Hiperparatiroidismo/cirugía , Aloinjertos , Hiperparatiroidismo Secundario/cirugía , Hiperparatiroidismo Secundario/complicaciones , Hormona ParatiroideaRESUMEN
This is a case of primary hyperparathyroidism in a female teenager with multiple fractures and severe bone manifestations. The histopathology revealed atypical parathyroid adenoma, an exceedingly rare form of hyperparathyroidism; its main differential diagnosis is parathyroid carcinoma, as it shares both clinical and histological characteristics with it, in addition to its still uncertain malignant potential.
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Hiperparatiroidismo , Neoplasias de las Paratiroides , Humanos , Adolescente , Femenino , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/patología , Huesos/patologíaAsunto(s)
Colina , Hiperparatiroidismo Secundario , Radiofármacos , Humanos , Colina/análogos & derivados , Hiperparatiroidismo Secundario/diagnóstico por imagen , Hiperparatiroidismo Secundario/sangre , Radioisótopos de Flúor , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Hiperparatiroidismo/diagnóstico por imagen , Hiperparatiroidismo/sangreRESUMEN
INTRODUCTION: The causal relationship between hyperparathyroidism and kidney graft dysfunction remains inconclusive. Applying Bradford-Hill's temporality and consistency causation principles, we assessed the effect of parathyroid hormone (iPTH) on graft histology and eGFR trajectory on kidney transplant recipients (KTRs) with normal time-zero graft biopsies. METHODS: Retrospective cohort study evaluating the effect of hyperparathyroidism on interstitial fibrosis and tubular atrophy (IF/TA) development in 1232 graft biopsies. Pre-transplant hyperparathyroidism was categorized by KDIGO or KDOQI criteria, and post-transplant hyperparathyroidism by iPTH >1× and >2× the URL 1 year after transplantation. RESULTS: We included 325 KTRs (56% female, age 38 ± 13 years, follow-up 4.2 years [IQR: 2.7-5.8]). Based on pre-transplant iPTH levels, 26% and 66% exceeded the KDIGO and KDOQI targets, respectively. There were no significant differences in the development of >25% IF/TA between KTRs with pre-transplant iPTH levels above and within target range according to KDIGO (53% vs. 62%, P = .16, HR.94 [95% CI:.67-1.32]) and KDOQI (60% vs. 60%, P = 1.0, HR 1.19 [95% CI:.88-1.60]) criteria. Similarly, there were no differences when using 1 year post-transplant iPTH cut-offs > 88 pg/mL (58% vs. 64%, P = .33) and > 176 pg/mL (55% vs. 62%, P = .19). After adjusting for confounders, no significant differences were observed in eGFR trajectories among the iPTH strata. CONCLUSION: In young KTRs who received a healthy graft, no association was found between increased pre- and post-transplant iPTH levels and graft dysfunction, as assessed histologically and through eGFR trajectory. The concept of hyperparathyroidism as a risk factor for graft dysfunction in recipients at low risk requires reevaluation.
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Aloinjertos , Tasa de Filtración Glomerular , Rechazo de Injerto , Supervivencia de Injerto , Hiperparatiroidismo , Trasplante de Riñón , Complicaciones Posoperatorias , Humanos , Trasplante de Riñón/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Adulto , Estudios de Seguimiento , Hiperparatiroidismo/etiología , Hiperparatiroidismo/patología , Pronóstico , Factores de Riesgo , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Aloinjertos/patología , Complicaciones Posoperatorias/etiología , Pruebas de Función Renal , Fallo Renal Crónico/cirugía , Persona de Mediana Edad , Hormona Paratiroidea/sangreRESUMEN
BACKGROUND: Bariatric procedures are associated with nutrient deficiencies. Studies show an association between gastric bypass (Roux-en-Y gastric bypass [RYGB]) and hypovitaminosis D as well as hyperparathyroidism, yet few compare RYGB to sleeve gastrectomy (SG), and large long-term analyses are scarce. OBJECTIVE: Evaluate trends of vitamin D and parathyroid hormone (PTH) levels in RYGB and SG. SETTING: National quality register. METHOD: The Scandinavian Obesity Surgery Registry records all bariatric surgeries in Sweden. Data from 2008 to 2021 on primary RYGB or SG with reported 25-hydroxy vitamin D (25-OH-D) and/or PTH levels were included. Individuals with an estimated glomerular filtration rate of <60 mL/min/1.73 m2 were excluded, leaving a study population of 25,385 RYGB and 5073 SG patients. RESULTS: A decrease in 25-OH-D, mirrored by an increase in PTH, was observed after the first year for both procedures, but more pronounced in RYGB. At 5 years, 25-OH-D levels were still higher than at baseline. Regular supplementation resulted in better 25-OH-D and PTH levels. Linear regression found that procedure type (RYGB versus SG), 25-OH-D levels, and time since surgery were significant factors in predicting PTH levels. The risk of pathologic PTH levels (>7 pmol/L) at 2 and 5 years postoperatively was roughly three times higher in RYGB (odds ratios = 3.41 and 2.84, respectively). CONCLUSIONS: Previous studies alongside these results suggest that RYGB, more so than SG, may cause hypovitaminosis D and thereby hyperparathyroidism, which could lead to osteopenia. The threshold for 25-OH-D should be >75 nmol/L, and despite higher levels, current vitamin D supplementation may not be sufficient. Follow-up should include screening for hyperparathyroidism and hypovitaminosis D.
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Gastrectomía , Derivación Gástrica , Obesidad Mórbida , Deficiencia de Vitamina D , Vitamina D , Humanos , Derivación Gástrica/efectos adversos , Gastrectomía/efectos adversos , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/sangre , Femenino , Masculino , Adulto , Persona de Mediana Edad , Estudios de Seguimiento , Vitamina D/sangre , Vitamina D/análogos & derivados , Obesidad Mórbida/cirugía , Obesidad Mórbida/complicaciones , Obesidad Mórbida/sangre , Suecia/epidemiología , Hormona Paratiroidea/sangre , Hiperparatiroidismo/etiología , Hiperparatiroidismo/sangre , Hiperparatiroidismo/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/sangre , Sistema de RegistrosAsunto(s)
Hiperparatiroidismo , Osteoclastos , Humanos , Médula Ósea , Osteoblastos , Huesos , Hiperparatiroidismo/complicacionesRESUMEN
Hyperparathyroidism (HPT) manifests as a complex condition with a substantial disease burden. While advances have been made in surgical interventions and non-surgical pharmacotherapy for the management of hyperparathyroidism, radical options to halt underlying disease progression remain lacking. Identifying putative genetic drivers and exploring novel drug targets that can impede HPT progression remain critical unmet needs. A Mendelian randomization (MR) analysis was performed to uncover putative therapeutic targets implicated in hyperparathyroidism pathology. Cis-expression quantitative trait loci (cis-eQTL) data serving as genetic instrumental variables were obtained from the eQTLGen Consortium and Genotype-Tissue Expression (GTEx) portal. Hyperparathyroidism summary statistics for single nucleotide polymorphism (SNP) associations were sourced from the FinnGen study (5590 cases; 361,988 controls). Colocalization analysis was performed to determine the probability of shared causal variants underlying SNP-hyperparathyroidism and SNP-eQTL links. Five drug targets (CMKLR1, FSTL1, IGSF11, PIK3C3 and SLC40A1) showed significant causation with hyperparathyroidism in both eQTLGen and GTEx cohorts by MR analysis. Specifically, phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3) and solute carrier family 40 member 1 (SLC40A1) showed strong evidence of colocalization with HPT. Multivariable MR and Phenome-Wide Association Study analyses indicated these two targets were not associated with other traits. Additionally, drug prediction analysis implies the potential of these two targets for future clinical applications. This study identifies PIK3C3 and SLC40A1 as potential genetically proxied druggable genes and promising therapeutic targets for hyperparathyroidism. Targeting PIK3C3 and SLC40A1 may offer effective novel pharmacotherapies for impeding hyperparathyroidism progression and reducing disease risk. These findings provide preliminary genetic insight into underlying drivers amenable to therapeutic manipulation, though further investigation is imperative to validate translational potential from preclinical models through clinical applications.
Asunto(s)
Proteínas Relacionadas con la Folistatina , Hiperparatiroidismo , Humanos , Análisis de la Aleatorización Mendeliana , Sitios de Carácter Cuantitativo/genética , Fosfatidilinositol 3-Quinasas Clase III , Costo de Enfermedad , Estudio de Asociación del Genoma CompletoRESUMEN
Context: Although a monoallelic mutation in the calcium-sensing receptor (CASR) gene causes familial hypocalciuric hypercalcemia (FHH), the functional characterization of the identified CASR mutation linked to the clinical response to calcimimetics therapy is still limited. Objective: A 45-year-old male presenting with moderate hypercalcemia, hypocalciuria, and inappropriately high parathyroid hormone (PTH) had a good response to cinacalcet (total serum calcium (Ca2+) from 12.5 to 10.1 mg/dl). We identified the genetic mutation and characterized the functional and pathophysiological mechanisms, and then linked the mutation to calcimimetics treatment in vitro. Design: Sanger sequencing of the CASR, GNA11, and AP2S1 genes was performed in his family. The simulation model was used to predict the function of the identified mutant. In vitro studies, including immunoblotting, immunofluorescence, a cycloheximide chase study, Calbryte™ 520 Ca2+ detection, and half-maximal effective concentration (EC50), were examined. Results: This proband was found to carry a de novo heterozygous missense I554N in the cysteine-rich domain of CASR, which was pathogenic based on the different software prediction models and ACGME criteria. The simulation model showed that CASR I554N mutation decreased its binding energy with Ca2+. Human CASR I554N mutation attenuated the stability of CASR protein, reduced the expression of p-ERK 1/2, and blunted the intracellular Ca2+ response to gradient extracellular Ca2+ (eCa2+) concentration. The EC50 study also demonstrated the correctable effect of calcimimetics on the function of the CASR I554N mutation. Conclusion: This novel CASR I554N mutation causing FHH attenuates CASR stability, its binding affinity with Ca2+, and the response to eCa2+ corrected by therapeutic calcimimetics.
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Hipercalcemia , Hipercalcemia/congénito , Hiperparatiroidismo , Enfermedades Renales , Masculino , Humanos , Persona de Mediana Edad , Hipercalcemia/tratamiento farmacológico , Hipercalcemia/genética , Hipercalcemia/diagnóstico , Receptores Sensibles al Calcio/genética , Receptores Sensibles al Calcio/metabolismo , Calcio/metabolismo , MutaciónRESUMEN
There is no consensus on the physiologic decline in estimated glomerular filtration rate (GFR) due to geriatric conditions related with the aging or chronic kidney disease (CKD) itself. In this study, we aimed to compare the CKD progression and associated complications in a large sample of geriatric and non-geriatric patients. The data of in 506 patients at age between 30 to 90 years and diagnosed with CKD at stage 2 and above (15 mL/min/1.73 m2â ≤â eGFRâ <â 90 mL/min/1.73 m2) were collected retrospectively and compared among geriatric (>65 years old) and non-geriatric individuals. The rate of hypertension was higher in geriatrics compared to non-geriatrics (96.6% vs 91.9%, Pâ =â .04). Among laboratory findings, only PTH level was significantly lower and HCO3 concentration was higher in geriatrics compared to non-geriatrics (Pâ =â .02, Pâ <â .001, respectively). There was no significant difference in last measured eGFR (Pâ =â .99) while that measured 4 years ago was lower in geriatrics compared to that of non-geriatrics (Pâ <â .001). eGFR change was smaller in geriatrics compared to non-geriatrics (Pâ <â .001), and rate of progressive renal disease among non-geriatric group (39%) was found to be significantly higher than in the geriatrics (17.2%) (Pâ <â .001). The prevalence of hyperkalemia was lower in geriatrics at stage 3a (Pâ =â .02); prevalence of hyperparathyroidism was lower in those at stage 3b (Pâ =â .02) and lastly the acidosis was observed significantly lower in geriatric patients at stage 3a, 3b, and 4 compared to the non-geriatrics at corresponding stages (Pâ <â .001, Pâ =â .03, and Pâ =â .04, respectively). The eGFR change was significantly smaller in geriatrics at stage 3b and 4 (Pâ <â .001 and Pâ =â .04, respectively) while the rate of progressed renal disease was lower in geriatrics at stage 3a and 3b (21.1% vs 9.9%, Pâ =â .03 and 41.2% vs 11.1%, Pâ <â .001, respectively). eGFR change in 4-year period and the rates of progressive renal disease are higher in the non-geriatrics and also the prevalence of secondary complications of CKD, such as hyperparathyroidism, acidosis, and hyperkalemia, are higher in non-geriatrics. This may reflect that decline of GFR in geriatric individuals is at least partially related to physiological aging rather than kidney disease. Therefore, devising age related CKD definitions might be appropriate.
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Acidosis , Hiperpotasemia , Hiperparatiroidismo , Insuficiencia Renal Crónica , Humanos , Anciano , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Retrospectivos , Hiperpotasemia/complicaciones , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/complicaciones , Tasa de Filtración Glomerular , Acidosis/etiología , Acidosis/complicaciones , Hiperparatiroidismo/complicaciones , Progresión de la EnfermedadRESUMEN
INTRODUCTION: Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post-transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients. METHODS: In this single-center study, retrospective data were collected on 88 children from 2013 to 2019. Data collected included dialysis vintage, biochemical parameters, post-transplant trends in iPTH, 25(OH)Vitamin D levels and estimated glomerular filtration rate (eGFR ml/min/1.73 m2 ). Pre-transplant treatment for HPT was quantified with a Treatment Burden score (TB, score range: 0-100). After log-transforming skewed variables (iPTH and eGFR), multivariable linear regression was performed to determine predictors of log {iPTH} at 6 and 36 months (mo) post-transplant. RESULTS: Median age was 12.8 (range: 1.9-20.5) years, and dialysis vintage was 11.2 (range: 0.0-112.9) months. The majority were of Hispanic and African Ancestry (77.3%). Median post-transplant iPTH was 69.5 (range: 1.8-306.8) pg/ml at 6 mo with a gradual downward trend to 59.0 (range: 28.0-445.0) pg/ml at 36 mo. Significant multivariable predictors of higher log {iPTH} post-transplant included longer dialysis vintage, higher TB, and lower log{eGFR} at 6 mo, and higher TB, lower log{eGFR}, and deceased donor transplant at 36 mo. CONCLUSIONS: Recognition of risk factors for HPT and monitoring iPTH post-transplant may facilitate timely interventions to mitigate cardiovascular and bone disease in pediatric KTx recipients. KEY MESSAGE: Describe serial trends in intact PTH after kidney transplantation. Pre- and post-transplant factors that contribute to persistence or re-occurrence of hyperparathyroidism after kidney transplantation in children include longer dialysis vintage, high pre-transplant treatment burden and decreased post-transplant GFR. Recognition of these factors, and monitoring intact PTH after kidney transplantation, could facilitate timely interventions to mitigate cardiovascular and bone disease in children.
Asunto(s)
Enfermedades Óseas Metabólicas , Hiperparatiroidismo , Trasplante de Riñón , Niño , Humanos , Hispánicos o Latinos , Hiperparatiroidismo/etiología , Trasplante de Riñón/efectos adversos , Hormona Paratiroidea , Estudios Retrospectivos , Lactante , Preescolar , Adolescente , Adulto Joven , Población NegraRESUMEN
The impact of pre-transplant parathyroid hormone (PTH) levels on early or long-term kidney function after kidney transplantation is subject of debate. We assessed whether severe hyperparathyroidism is associated with delayed graft function (DGF), death-censored graft failure (DCGF), or all-cause mortality. In this single-center cohort study, we studied the relationship between PTH and other parameters related to bone and mineral metabolism, including serum alkaline phosphatase (ALP) at time of transplantation with the subsequent risk of DGF, DCGF and all-cause mortality using multivariable logistic and Cox regression analyses. In 1,576 kidney transplant recipients (51.6 ± 14.0 years, 57.3% male), severe hyperparathyroidism characterized by pre-transplant PTH ≥771 pg/mL (>9 times the upper limit) was present in 121 patients. During 5.2 [0.2-30.0] years follow-up, 278 (15.7%) patients developed DGF, 150 (9.9%) DCGF and 432 (28.6%) died. A higher pre-transplant PTH was not associated with DGF (HR 1.06 [0.90-1.25]), DCGF (HR 0.98 [0.87-1.13]), or all-cause mortality (HR 1.02 [0.93-1.11]). Results were consistent in sensitivity analyses. The same applied to other parameters related to bone and mineral metabolism, including ALP. Severe pre-transplant hyperparathyroidism was not associated with an increased risk of DGF, DCGF or all-cause mortality, not supporting the need of correction before kidney transplantation to improve graft or patient survival.
Asunto(s)
Hiperparatiroidismo , Trasplante de Riñón , Humanos , Masculino , Femenino , Trasplante de Riñón/efectos adversos , Estudios de Cohortes , Hiperparatiroidismo/complicaciones , Hormona Paratiroidea , Minerales , Supervivencia de Injerto , Factores de Riesgo , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto , Estudios RetrospectivosRESUMEN
OBJECTIVE: To prospectively evaluate the outcomes of ultrasound (US)-guided radiofrequency ablation (RFA) in tertiary hyperparathyroidism (THPT). MATERIALS AND METHODS: Patients with THPT underwent RFA between September 2017 and January 2022. Laboratory parameters, including serum intact parathyroid hormone (iPTH) levels, were monitored for 48 months after RFA and compared with the levels at baseline. Complications related to RFA and changes in hyperparathyroidism-related clinical symptoms were recorded before and after RFA. RESULTS: A total of 42 patients with THPT were recruited for this study. Ultimately, 36 patients with renal failure and 2 patients who underwent successful renal transplantation (male:female, 17:21; median age, 54.5 years) were enrolled. The follow-up time was 21.5 ± 19.0 months in the 36 patients with renal failure. In these 36 patients, iPTH levels were significantly decreased to 261.1 pg/mL at 48 months compared with the baseline value of 1284.9 pg/mL (P = 0.012). Persistent hyperparathyroidism, defined as iPTH levels maintained at > 585.0 pg/mL for 6 months after treatment, occurred in 4.0% of patients (1/25). Recurrent hyperparathyroidism, defined as iPTH levels > 585.0 pg/mL after 6 months, were 4.0% (1/25) and 0.0% (0/9) at 6 months and 4 years after treatment, respectively. In two patients with THPT after successful renal transplantation, iPTH decreased from the baseline value of 242.5 and 115.9 pg/mL to 171.0 and 62.0 pg/mL at 6 months after treatment. All complications resolved within 6 months of ablation without medical intervention, except in 10.5% (4/38) patients with permanent hypocalcemia. The overall symptom recovery rate was 58.8% (10/17). The severity scores for bone pain, arthralgia, and itchy skin associated with hyperparathyroidism improved after treatment (P < 0.05). CONCLUSION: US-guided RFA is an effective and safe alternative to surgery in the treatment of patients with TPTH and improves hyperparathyroidism-related clinical symptoms.