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1.
Adv Exp Med Biol ; 1226: 37-50, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32030674

RESUMO

Parathyroid tumors are the second most common endocrine neoplasia, and it is almost always associated with hypersecretion of the parathormone (PTH), involved in calcium homeostasis, causing primary hyperparathyroidism (PHPT). Parathyroid neoplasia has a stromal component particularly represented in atypical adenomatous and carcinomatous lesions. Recently, data about the features and the function of the parathyroid tumor microenvironment (TME) have been accumulated. Parathyroid TME includes heterogeneous cells: endothelial cells, myofibroblasts, lymphocytes and macrophages, and mesenchymal stem cells have been identified, each of them presenting a phenotype consistent with tumor-associated cells. Parathyroid tumors overexpress proangiogenic molecules including vascular endothelial growth factor (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietins that promote both recruitment and proliferation of endothelial cell precursors, thus resulting in a microvessel density higher than that detected in normal parathyroid glands. Moreover, parathyroid tumor endocrine cells operate multifaceted interactions with stromal cells, partly mediated by the CXCL12/CXCR4 pathway, while, at present, the immune landscape of parathyroid tumors has just begun to be investigated. Studies about TME in parathyroid adenomas provide an example of the role of TME in benign tumors, whose molecular mechanisms and functions comprehension are limited.


Assuntos
Neoplasias das Paratireoides/metabolismo , Neoplasias das Paratireoides/patologia , Microambiente Tumoral , Humanos , Glândulas Paratireoides/metabolismo , Glândulas Paratireoides/patologia , Hormônio Paratireóideo/metabolismo
2.
Anticancer Res ; 40(1): 535-543, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892609

RESUMO

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.


Assuntos
Suplementos Nutricionais , Genômica , Metabolômica , Vitamina D/farmacologia , Adulto , Relação Dose-Resposta a Droga , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Hormônio Paratireóideo/sangue , Análise de Componente Principal , Mapas de Interação de Proteínas/efeitos dos fármacos , Vitamina D/análogos & derivados , Vitamina D/sangue
3.
Praxis (Bern 1994) ; 109(1): 35-41, 2020 Jan.
Artigo em Alemão | MEDLINE | ID: mdl-31910762

RESUMO

CME: Hypercalcemia Abstract. Hypercalcemia is defined as albumin-corrected calcium >2.6 mmol/l. Symptoms of hypercalcemia are mainly neurological-psychiatrical and cardiovascular. Severe symptomatic hypercalcemia is an emergency and requires an immediate therapy. At the same time, the underlying cause of hypercalcemia has to be identified and treated. Based on pathophysiology, hypercalcemia can be divided into four groups: parathyroid hormone dysfunction, disturbances of vitamin D metabolism, of bone metabolism or of renal calcium excretion. Medical history and specific laboratory diagnostics help to identify one of these groups and to make the correct final diagnosis.


Assuntos
Hipercalcemia , Cálcio/metabolismo , Cálcio na Dieta , Emergências , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/etiologia , Hormônio Paratireóideo
4.
Ann Otol Rhinol Laryngol ; 129(1): 70-77, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31510765

RESUMO

OBJECTIVE: Prediction and early intervention for hypocalcemia following parathyroidectomy and total thyroidectomy can decrease hospital cost and prevent severe hypocalcemia-related complications. This study aims to predict the severity of hypocalcemia after parathyroidectomy or thyroidectomy and to stratify patients into groups with different levels of risk for developing severe hypocalcemia, so that higher risk patients may be monitored more closely and receive earlier interventions. METHODS: This was a retrospective cohort study of 100 patients with primary hyperparathyroidism who underwent parathyroidectomy as the primary treatment modality at a tertiary care hospital. Clinical information, including demographic information, perioperative PTH and calcium levels, vitamin D levels, weight of the pathologic glands removed, gland pathology, and re-admission rates, were retrieved. Statistical analysis was performed to analyze the association between collected variables and percentage of calcium drop following parathyroidectomy with statistical significant set at P-values <0.05. RESULTS: Age, sex, and vitamin D level provided very minimal information to quantify risks of postoperative hypocalcemia. The percentage of decrease from preoperative PTH level to the lowest PTH level after the removal of the abnormal gland(s) is the most significant predicting factor for the severity of postoperative hypocalcemia. There is a mathematic regressional correlation between them. A formula was generated to quantify this linear relationship between them, and the nadir calcium can be calculated as Canadir=Capreop*[1-0.35*(PTHpreop-PTHintraop)2PTHpreop2], where Canadir = the lowest postoperative calcium level, and PTHintraop = PTH level 15 minutes after removal of the abnormal gland, with the value of R2 > 0.7. The formula has been tested primarily in our patient population with good reliability. CONCLUSIONS: The highest preoperative, lowest postoperative, and change in PTH level can help us reliably calculate the trend of postoperative calcium level. Decision to pursue early interventions can be made based on the calculated result from the formula we obtained.


Assuntos
Hiperparatireoidismo Primário/cirurgia , Hipocalcemia/epidemiologia , Paratireoidectomia , Complicações Pós-Operatórias/epidemiologia , Adenoma/sangue , Adenoma/patologia , Adenoma/cirurgia , Adulto , Fatores Etários , Feminino , Humanos , Hiperparatireoidismo Primário/sangue , Hipocalcemia/sangue , Hipocalcemia/terapia , Período Intraoperatório , Magnésio/sangue , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Complicações Pós-Operatórias/sangue , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Tireoidectomia , Carga Tumoral , Vitamina D/sangue
5.
BMC Infect Dis ; 19(1): 1020, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791247

RESUMO

BACKGROUND: Vitamin D deficiency, determined by blood levels of 25-hydroxyvitamin D [25(OH) D, i.e. the major vitamin D form in blood], has been shown to associate with all-cause mortalities. We recently demonstrated that blood levels of 1,25-dihydroxyvitamin D [1,25(OH)2D, i.e. the active vitamin D] were significantly lower in non-survivors compared to survivors among sepsis patients. Unexpectedly, despite the well documented roles of 1,25(OH)2D in multiple biological functions such as regulation of immune responses, stimulation of antimicrobials, and maintenance of barrier function, 1,25(OH)2D supplementation failed to improve disease outcomes. These previous findings suggest that, in addition to 1,25(OH)2D deficiency, disorders leading to the 1,25(OH)2D deficiency also contribute to mortality among sepsis patients. Therefore, this study investigated the mechanisms leading to sepsis-associated 1,25(OH)2D deficiency. METHODS: We studied mechanisms known to regulate kidney 25-hydroxylvitamin D 1α-hydroxylase which physiologically catalyzes the conversion of 25(OH) D into 1,25(OH)2D. Such mechanisms included parathyroid hormone (PTH), insulin-like growth factor 1 (IGF-1), fibroblast growth factor 23 (FGF-23), and kidney function. RESULTS: We demonstrated in both human subjects and mice that sepsis-associated 1,25(OH)2D deficiency could not be overcome by increased production of PTH which stimulates 1α-hydroxylase. Further studies showed that this failure of PTH to maintain blood 1,25(OH)2D levels was associated with decreased blood levels of IGF-1, increased blood levels of FGF-23, and kidney failure. Since the increase in blood levels of FGF-23 is known to associate with kidney failure, we further investigated the mechanisms leading to sepsis-induced decrease in blood levels of IGF-1. Our data showed that blood levels of growth hormone, which stimulates IGF-1 production in liver, were increased but could not overcome the IGF-1 deficiency. Additionally, we found that the inability of growth hormone to restore the IGF-1 deficiency was associated with suppressed expression and signaling of growth hormone receptor in liver. CONCLUSIONS: Because FGF-23 and IGF-1 have multiple biological functions besides their role in regulating kidney 1α-hydroxylase, our data suggest that FGF-23 and IGF-1 are warranted for further investigation as potential agents for the correction of 1,25(OH)2D deficiency and for the improvement of survival among sepsis patients.


Assuntos
Sepse/sangue , Sepse/complicações , Deficiência de Vitamina D/etiologia , Vitamina D/análogos & derivados , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Fator de Crescimento Insulin-Like I , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hormônio Paratireóideo/sangue , Sepse/fisiopatologia , Transdução de Sinais , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/fisiopatologia
6.
Wiad Lek ; 72(11 cz 2): 2202-2209, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31860837

RESUMO

OBJECTIVE: Introduction: Mineral homeostasis is achieved through a complex interplay of several feedback processes involving primarily the bone, intestine and kidney, regulated by different proteins acting on endocrine, paracrine or autocrine levels. The dysregulation of these processes in chronic renal failure, called kidney disease (CKD) - mineral and bone disorder (CKD-MBD), although apparent, is still poorly understood. The aim: The aim of the study was an analysis of potential relationships between selected biomarkers of CKD-MBD in maintenance hemodialysis (HD) patients. PATIENTS AND METHODS: Material and Methods: In the first part of this cross-sectional study, the 25(OH)D serum concentrations were measured in 115 HD vitamin D naïve patients from 5 dialysis units located in central Poland. Thereafter in 81 patients (49 men, 32 women, aged 67 ± 13 years) with vitamin deficiency (25(OH)D <20 ng/ml) serum concentrations of 25(OH)D, 1,25(OH)2D, intact parathyroid hormone (iPTH), intact FGF23, sclerostin (SCL), osteocalcin (OC), and C-terminal telopeptide of type I collagen (CTX1) were determined. RESULTS: Results: Serum levels of both 25(OH)D and 1,25(OH)2D were low (mean values 13.4±6.72 ng/ml and 12.9 ± 9.08 pmol/l, respectively). While serum 25(OH)D correlated only with a declared time spent outside (r= 0.411; p=0.000139), serum 1,25(OH)2D was related to diuresis (r= 0.289; p=0.009), and negatively to time on dialysis (r= -0.272; p=0.014) , serum phosphate (r= -0.393; p=0.000289), FGF23(r= -0.295; p=0.008), and SCL (r= -0.260; p=0.019). There was a marked dispersion of FGF-23 serum levels across the group (mean 823±5647, median 379 pg/ml) , and - as expected - they correlated highly with phosphate (r= 0.549, p=0.000), calcium (r= 0,328, p=0,003), OC (r=0.479; p=0.000), and negatively with z 1,25(OH)2D (r= -0.295, p=0.008). Mean serum SCL levels (89.2±46.7, median 81.9 pmol/l) were 3x higher than in general population, and correlated highly positively with dialysis vintage (r=0.402; p<0.001), age (r=0.356; p=0.001), as well as negatively with 1,25(OH)2D (r= -0.260; p=0.019) and CTX1 (r= -0.293; p=0.008). CONCLUSION: Conclusions: In our hemodialysis population, in addition to profoundly impaired 1,25(OH)2D synthesis, there is also a widespread prevalence of 25(OH)D deficiency. The patients have also markedly increased serum bone-secreted proteins, FGF23, and SCL, which regulate mineral and bone metabolism and are associated with the systemic side effects of uremia. All these hormones interact one with the other, creating a sophisticated cross-talk between the bone, intestine, and the kidney.


Assuntos
Deficiência de Vitamina D , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Remodelação Óssea , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo , Polônia , Diálise Renal , Vitamina D
7.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(12): 924-927, 2019 Dec 07.
Artigo em Chinês | MEDLINE | ID: mdl-31887819

RESUMO

Objective: To investigate the etiology, characteristics and prevention of severe facial deformity in patients with uremia entering the dialysis stage. Methods: Four cases with uremia in the dialysis stage who presented with severe facial deformity between October 2011 and November 2018 were reviewed, including 3 males and 1 female. The ages were 31, 15, 51 and 61, respectively. The general information, clinical symptoms, biochemical indicators, relevant imaging indicators, diagnoses, treatments and efficacies of the 4 patients admitted to the First Affiliated Hospital of Anhui Medical University were collected. Results: All the 4 patients appeared obviously shorter, accompanied by a certain degree of decline in self-care ability, multiple bone and joint pain and severe facial deformity. They presented with significantly increased serum levels of alkaline phosphatase, calcium, phosphorus and parathyroid hormone, and parathyroid hormone level>2 500 pg/ml.Ultrasonography and (99)Tc(m) radionuclide scan showed in situ or ectopic hyperplasia of parathyroid tissue. Bone radiography showed local decrease of bone mineral density and cystic changes.After parathyroidectomy, the serum levels of alkaline phosphatase, parathyroid hormone, calciumand phosphorus decreased significantly, while bone pain symptoms and facial deformities gradually improved. Conclusion: Secondary hyperparathyroidism is a serious complication in patients with dialysis and few of patients may have severe facial deformity (Sagliker syndrome) affecting their normal life and social activities. Parathyroidectomy can improve the facial deformity and the quality of life of patients.


Assuntos
Hiperparatireoidismo Secundário , Uremia , Adolescente , Adulto , Cálcio , Feminino , Humanos , Hiperparatireoidismo Secundário/complicações , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides , Hormônio Paratireóideo , Paratireoidectomia , Qualidade de Vida , Uremia/complicações
8.
Chirurgia (Bucur) ; 114(5): 564-570, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670631

RESUMO

The complications of thyroidectomy vary from hypocalcemia and recurrent laryngeal nerve lesions to injury of vocal folds, local hematoma, cysts, granuloma. Post-operative hypocalcemia has an incidence of 1.2-40%. Permanent hyoparathyroidism is registered in 3% of cases. This is a brief narrative review focusing on the levels of calcium after performing a thyroidectomy and the need of calcium supplements under these circumstances. This complication, even it seems rather harmless at first, in fact it represents an important contributor to hospitalization delay and, especially for severe forms, to poor quality of life, including the risk of life threatening episodes. Devascularisation of parathyroid glands in addition to injury or dissection causes hypoparathyroidism. Hypocalcemia risk differs with sex (females have a higher risk), lymph node dissection (it increases the risk), it differs with type of thyroidectomy (larger dissections have a higher risk; also the intervention for recurrent goitre and second intervention for post-operatory bleeding increase the risk of hypocalcemia; while Basedow disease is probably at higher risk than multinodular goitre among benign conditions) and the duration of procedure. Pre-operatory low calcium, parathormon (PTH), 25-hydroxivitamin D increases the risk. The calcium drop rate matters as well: a decrease of 1 mg/dL calcium over 12 hours after surgery is independently correlated with the risk of symptomatic hypocalcemia. Early post-operatory PTH and calcium are best predictors for the need of oral calcium supplements. Routine post-operatory calcium and vitamin D supplementation statistically significant decreases the risk of developing transitory hypocalcemia and acute complications compare to calcium alone supplements or no supplements. In cases of hypoparathyroidism calcitriol is preferred.


Assuntos
Hipocalcemia/terapia , Tireoidectomia/efeitos adversos , Cálcio/sangue , Humanos , Hipocalcemia/sangue , Hipocalcemia/etiologia , Hipoparatireoidismo/sangue , Hipoparatireoidismo/tratamento farmacológico , Hipoparatireoidismo/etiologia , Hormônio Paratireóideo/sangue , Qualidade de Vida , Fatores de Risco , Resultado do Tratamento
9.
Klin Lab Diagn ; 64(11): 673-676, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31747496

RESUMO

The aim was to study the level of some cytokines (IL-2, IL-6, IL-8 TNFα) and calcium regulating hormones (calcitonin, parathyroid hormone, 25 (OH) D) in the blood of patients with rheumatoid arthritis (RA) depending on rheumatoid factor (RF) and the assessment of the role of the revealed violations in the pathogenesis of bone loss in this pathology. For this purpose, 74 patients with RA (59 women, 15 men) aged from 27 to 71 were examined. On the basis of RF in the blood serum, the patients were divided into 2 groups: seronegative and seropositive RA. The control group included 16 healthy individuals (13 women, 3 men). The results obtained that the serological variant of RA affects the serum levels of proinflammatory cytokines and calcium-regulating hormones: more pronounced changes were found in seropositive RA. The high production of IL-2, IL-6, IL-8, TNF-α and parathyroid hormone detected in both groups of patients undoubtedly contributes to the mechanisms of bone loss in RA. In both groups we detected hypovitaminosis D. This results recommended to use this vitamin in the complex treatment of RA.


Assuntos
Artrite Reumatoide/sangue , Calcitonina/sangue , Citocinas/sangue , Hormônio Paratireóideo/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator Reumatoide , Vitamina D/sangue
10.
Expert Opin Pharmacother ; 20(17): 2081-2093, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31675257

RESUMO

Introduction: Extended-release calcifediol (ERC) is an orally administered prohormone of active vitamin D (1,25-dihydroxyvitamin D [1,25D]) designed to safely and sufficiently increase serum total 25-hydroxyvitamin D (25D) to reduce elevated parathyroid hormone (PTH) in patients with non-dialysis-chronic kidney disease (ND-CKD). ERC is currently approved in the United States and Canada.Areas covered: Herein, key clinical data relating to the pharmacokinetics, pharmacodynamics, efficacy and safety of ERC are reviewed.Expert opinion: Currently available treatment options for secondary hyperparathyroidism (SHPT) in ND-CKD have limitations: the effectiveness of nutritional vitamin D supplements for reduction of PTH levels is unproven and active (1α-hydroxylated) vitamin D analogues elevate serum calcium, which increases the risk of hypercalcemia and vascular calcification. Clinical studies show that ERC is an effective, well tolerated treatment for SHPT in ND-CKD. ERC gradually raises serum 25D levels, resulting in physiologically regulated increases in serum 1,25D and sustained reductions in PTH, while avoiding clinically meaningful increases in serum phosphorus, calcium and fibroblast growth factor 23. ERC offers a new, effective and well tolerated treatment option for the early management of SHPT in patients with ND-CKD.


Assuntos
Calcifediol/uso terapêutico , Distúrbio Mineral e Ósseo na Doença Renal Crônica/tratamento farmacológico , Calcifediol/efeitos adversos , Calcifediol/farmacocinética , Cálcio/sangue , Ensaios Clínicos como Assunto , Diarreia/etiologia , Meia-Vida , Humanos , Hormônio Paratireóideo/sangue , Resultado do Tratamento
11.
Am Surg ; 85(9): 939-943, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638503

RESUMO

Reoperative parathyroid surgery (REOPS) is often associated with lower cure rates and greater risk of nerve injury and hypoparathyroidism. The aim of this study was to evaluate cure rates, pathology, complications, and the efficacy of preoperative localization in patients requiring REOPS. Between 1992 and 2017, 2491 consecutive patients underwent parathyroidectomy for primary hyperparathyroidism. With Institutional Review Board approval, our prospectively collected parathyroidectomy outcomes database was queried for operative findings, outcomes, pathology, and localization methodology. Three hundred forty-six patients had REOPS (111 men/32% and 235 women/68%), with an overall cure rate of 91 per cent and a mean follow-up of 1.9 ± 0.7 years. The average preoperative serum calcium and parathyroid hormone were 11 ± 1 mg/dL and 373 ± 796 pg/mL, respectively. Normalization of intraoperative parathyroid hormone occurred in 248 patients and it was predictive of cure in 98.8 per cent of patients. A single adenoma was resected in 253 patients (75%), and the superior gland location was most common at 57 per cent. Ectopic glands were identified in only 33 patients. When preoperative imaging localized a lesion, a tumor was identified in that location in 75.4 per cent of sestamibi or SPECT/CT scans, 57.8 per cent of CT, 61.2 per cent of MRI, and 46.2 per cent of US. When at least two imaging modalities were concordant, sensitivity improved to 91.6 per cent (P < 0.001). Complication rates of permanent hypoparathyroidism and recurrent nerve palsy occurred in 0.03 per cent of patients. REOP for recurrent or persistent primary hyperparathyroidism has a cure rate of 91 per cent. Most missed parathyroid tumors are in the neck, and multimodal imaging improves preoperative localization and success.


Assuntos
Adenoma/cirurgia , Hiperparatireoidismo Primário/cirurgia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/métodos , Reoperação , Adenoma/sangue , Adenoma/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico por imagem , Hipoparatireoidismo , Masculino , Pessoa de Meia-Idade , Paralisia , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/diagnóstico por imagem , Paratireoidectomia/efeitos adversos , Complicações Pós-Operatórias , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio Tc 99m Sestamibi , Adulto Jovem
12.
Nat Commun ; 10(1): 4693, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619668

RESUMO

Extracellular phosphate regulates its own renal excretion by eliciting concentration-dependent secretion of parathyroid hormone (PTH). However, the phosphate-sensing mechanism remains unknown and requires elucidation for understanding the aetiology of secondary hyperparathyroidism in chronic kidney disease (CKD). The calcium-sensing receptor (CaSR) is the main controller of PTH secretion and here we show that raising phosphate concentration within the pathophysiologic range for CKD significantly inhibits CaSR activity via non-competitive antagonism. Mutation of residue R62 in anion binding site-1 abolishes phosphate-induced inhibition of CaSR. Further, pathophysiologic phosphate concentrations elicit rapid and reversible increases in PTH secretion from freshly-isolated human parathyroid cells consistent with a receptor-mediated action. The same effect is seen in wild-type murine parathyroid glands, but not in CaSR knockout glands. By sensing moderate changes in extracellular phosphate concentration, the CaSR represents a phosphate sensor in the parathyroid gland, explaining the stimulatory effect of phosphate on PTH secretion.


Assuntos
Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismo , Fosfatos/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Animais , Técnicas de Inativação de Genes , Células HEK293 , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/metabolismo , Camundongos , Mutação , Receptores de Detecção de Cálcio/genética , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/metabolismo
13.
Pan Afr Med J ; 33: 183, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565143

RESUMO

Introduction: There is a great scarcity of literature in Pakistan investigating the proportion of end stage renal disease (ESRD) patients undergoing hemodialysis (HD) who meet the recommended kidney diseases outcome quality initiative (K/DOQI) guidelines for serum calcium (Ca), phosphorus (P), calcium phosphorus product (Ca x P) and parathyroid hormone (PTH) levels. Our study aimed to determine frequencies of patients who met the K/DOQI targets for these minerals at a tertiary care hospital's dialysis unit. Methods: 111 ESRD patients on maintenance HD were selected from a tertiary care hospital. Serum Ca and P were assayed on chemistry analyser. PTH was measured through electrochemiluminescence sandwich method. Data were compared with K/DOQI targets and analysed using SPSS-21. Results: The mean age of patients was 55.85 years (SD ± 13.95). Gender distribution was almost equal with 49.5% males and 50.5% females. The patients had mean corrected serum Calcium 9.12 ± 0.64 mg/dL, Phosphorus 4.57 ± 1.54 mg/dL and Parathyroid hormone 333.8 ± 278.4 pg/mL. The patients had achieved K/DOQI target ranges of Ca, P, PTH, Ca x P product and all 4 criteria in 63.1%, 47.6%, 38.7%, 84.7% and 10.8% respectively. Conclusion: Majority of patients on maintenance HD at our institution did not achieve the recommended K/DOQI target ranges. Further studies pertaining to the Asian subcontinent will prove resourceful for comparison of mineral metabolism and dialysis outcome of ESRD patients.


Assuntos
Cálcio/sangue , Falência Renal Crônica/terapia , Hormônio Paratireóideo/sangue , Fósforo/sangue , Diálise Renal/métodos , Adulto , Idoso , Estudos Transversais , Técnicas Eletroquímicas , Feminino , Humanos , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Paquistão , Guias de Prática Clínica como Assunto , Centros de Atenção Terciária
14.
Prague Med Rep ; 120(2-3): 84-94, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31586507

RESUMO

Ageing is associated with the accumulation of damage to all the macromolecules within and outside cells leading to progressively more cellular and tissue defects and resulting in age-related frailty, disability and disease. As a result of the aging process the bone deteriorates in composition, structure and function. Age-related musculoskeletal losses are a major public health burden because they can cause physical disability and increased mortality. We tried to find out on a small set of old women, without risk factors for osteoporosis, what caused them the loss of bone minerals. All 492 women had just only one risk factor - the old age. Laboratory findings have shown a decreased serum C telopeptide and low serum alkaline phosphatase circulating markers, used to quantify bone resorption and formation, and very low level of vitamin D. Very low level of vitamin D that disrupted calcium absorption through the intestine, and decreased calcemia increased parathyroid hormone levels with resulting bone effect. The manifestation of physiological aging is worsening eyesight, peripheral neuropathy, depression, worsening of physical condition, skin aging, sarcopenia and bone mineral loss. Senile osteoporosis, which is not caused by known risk factors for osteoporosis, does not appear to be a separate disease, but is part of the physiological process of aging. Treatment of senile osteoporosis should be focused on the control of secondary hyperparathyroidism by administration of vitamin D and calcium. The risk of fractures in the advanced age is determined by a large number of factors ranging from hazards in the home environment to frailty and poor balance.


Assuntos
Envelhecimento/sangue , Envelhecimento/patologia , Fosfatase Alcalina/sangue , Densidade Óssea , Cálcio/metabolismo , Colágeno Tipo I/sangue , Feminino , Humanos , Osteogênese , Osteoporose/sangue , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Vitamina D/sangue
15.
Pol Merkur Lekarski ; 47(279): 103-105, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31557139

RESUMO

Hypercalcaemia is associated with a number of symptoms that appear in of various parts of body systems. Renal dysfunction or cardiovascular abnormalities present only a part of the multidirectional action of the disturbed calcium balance. It is important for every diagnosis to know the cause of this condition and the mechanism that is responsible in a given situation for the distribution of calcium ions. A CASE REPORT: Diagnosis presents the case of a 51-year-old woman with hypercalcaemia and thyrotoxicosis. The patient had been taking lithium preparations for 20 years, until she was hospitalized in the Department of Nephrology due to symptoms and poisoning confirmed biochemically with this substance. Dyselectrolytemia (hypernatremia, hypercalcaemia) and polydipsia, polyuria and a weight loss were found. According to the laboratory tests performed in the Department of Endocrinology, high levels of PTH in the blood, hypercalcaemia, normophosphataemia, normocalciuria, hypophosphaturia and normal renal function were found. In differential diagnosis, lithium poisoning or primary hyperparathyroidism (PHP) was considered to be the most likely pathomechanism of PTH-dependent hypercalcaemia, not to mention the possible effects of thyrotoxicosis. The patient underwent USG and MRI of the neck, followed by BACC selected by previous imaging of changes in the vicinity of the lower pole of the left thyroid lobe and focal lesions in the right thyroid lobe. After endocrinological diagnosis, the patient was provided with antithyroid drugs and directed to the Department of Nuclear Medicine with the aim of extend the diagnosis with scintigraphy of the parathyroid glands. CONCLUSIONS: As demonstrated by this case, differential diagnosis of hypercalcaemia and thyrotoxicosis is important. From a practical point of view, the causes of hypercalcaemia can be divided into primary hyperparathyroidism (PHP) and "all others", and among the causes of thyrotoxicosis, those less frequent should remembered. The variety of symptoms, potential causes and overlapping disease indicate the validity of individual approach to each patient.


Assuntos
Hipercalcemia , Hiperparatireoidismo Primário , Esquizofrenia Paranoide , Cálcio , Feminino , Humanos , Hipercalcemia/complicações , Hiperparatireoidismo Primário/complicações , Pessoa de Meia-Idade , Hormônio Paratireóideo , Esquizofrenia Paranoide/complicações
16.
Artigo em Inglês | MEDLINE | ID: mdl-31505801

RESUMO

A positive association between metabolic syndrome (MetS) and osteoporosis has been demonstrated in previous animal studies. The mechanisms of MetS in orchestrating the bone remodelling process have traditionally focused on the interactions between mature osteoblasts and osteoclasts, while the role of osteocytes is unexplored. Our earlier studies demonstrated the bone-promoting effects of tocotrienol using a rat model of osteoporosis induced by MetS. This study aimed to investigate the expression of osteocyte-derived peptides in the bone of rats with MetS-induced osteoporosis treated with tocotrienol. Age-matched male Wistar rats (12-week-old; n = 42) were divided into seven experimental groups. Two groups served as the baseline and normal group, respectively. The other five groups were fed with a high-carbohydrate high-fat (HCHF) diet to induce MetS. The five groups of HCHF animals were treated with tocopherol-stripped corn oil (vehicle), annatto tocotrienol (60 and 100 mg/kg), and palm tocotrienol (60 and 100 mg/kg) starting from week 8. At the end of the study, the rats were sacrificed and their right tibias were harvested. Protein was extracted from the metaphyseal region of the proximal right tibia and levels of bone peptides, including osteoprotegerin (OPG), soluble receptor activator of nuclear factor-kappa B ligand (sRANKL), sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH), were measured. The vehicle-treated animals displayed higher levels of sRANKL, SOST, DKK-1, FGF-23, and PTH as compared to the normal animals. Oral supplementation of annatto and palm tocotrienol (60 and 100 mg/kg) reduced the levels of sRANKL and FGF-23 in the HCHF animals. Only 100 mg/kg annatto and palm tocotrienol lowered SOST and DKK-1 levels in the HCHF animals. In conclusion, tocotrienol exerts potential skeletal-promoting benefit by modulating the levels of osteocytes-derived bone-related peptides.


Assuntos
Síndrome Metabólica/metabolismo , Osteoporose/metabolismo , Tíbia/efeitos dos fármacos , Tocotrienóis/farmacologia , Animais , Bixaceae , Proteínas Morfogenéticas Ósseas/metabolismo , Carotenoides , Modelos Animais de Doenças , Fatores de Crescimento de Fibroblastos/metabolismo , Marcadores Genéticos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Síndrome Metabólica/complicações , Osteócitos/efeitos dos fármacos , Osteócitos/metabolismo , Osteoporose/etiologia , Osteoprotegerina/metabolismo , Hormônio Paratireóideo/metabolismo , Extratos Vegetais , Ligante RANK/metabolismo , Ratos Wistar , Tíbia/metabolismo
17.
Braz Oral Res ; 33: e086, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31483052

RESUMO

Treatment of patients with bisphosphonate usage is a significant concern for oral surgeons because it interferes with jaw bone turnover and regeneration. In case of adverse effects manifesting related to bisphosphonate use, oral surgeons are usually treating and keep the patient's symptoms under control. In this study, we aimed to investigate a new treatment protocol for medication-related osteonecrosis of the jaw (MRONJ). This treatment protocol consisted of administering human parathyroid hormone (hPTH) loaded chitosan microspheres which were prepared by ionotropic gelation method or/and the prepared microspheres were suspended in a poloxamer gel. After in-vitro optimization studies, the efficacy of the chosen formulations was evaluated in-vivo studies. Zoledronic acid was administered daily to forty-eight adult female Sprague-Dawley rats, divided into four experimental groups, at a daily concentration of 0.11 mg/kg over three weeks to induce the MRONJ model. At the end of this period, maxillary left molar teeth were extracted. In the first group, the subjects received no treatment. In the negative control group, poloxamer hydrogel containing empty microspheres were immediately applied to the soft tissues surrounding the extraction socket. The treatment group-1 was treated with local injections of poloxamer hydrogel containing hPTH. The treatment group-2 was treated with a single local injection of poloxamer hydrogel containing hPTH-loaded chitosan microspheres. Both treatment groups received a total of 7 µg of hPTH at the end of the treatment protocol. Our study demonstrates successful attenuation of MRONJ through a local drug delivery system combined with hPTH, as opposed to previously attempted treatment strategies.


Assuntos
Conservadores da Densidade Óssea/farmacologia , Quitosana/farmacologia , Maxila/efeitos dos fármacos , Hormônio Paratireóideo/farmacologia , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Quitosana/uso terapêutico , Preparações de Ação Retardada , Feminino , Humanos , Maxila/patologia , Microesferas , Modelos Animais , Hormônio Paratireóideo/uso terapêutico , Poloxâmero/administração & dosagem , Poloxâmero/química , Ratos Sprague-Dawley , Ácido Zoledrônico/efeitos adversos
18.
Niger J Clin Pract ; 22(9): 1201-1207, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31489854

RESUMO

Background: The presence of vitamin D, and parathyroid hormone receptors has been demonstrated in the vascular endothelium. Variations in vitamin D, and parathyroid hormone levels may affect coronary flow and cause the coronary slow-flow phenomenon (CSF). Methods: We enrolled 93 patients who had undergone coronary angiography and had near-normal coronary arteries. Blood samples were taken to determine the calcium, phosphorus, 25-hydroxy vitamin D, and parathyroid hormone levels. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D level of less than 20 ng/mL. We divided the study population into two groups according to thrombolysis in myocardial infarction frame count (TFC) levels. Results: Patients with TFC ≤27 were in the control group (n = 39), and those with TFC >27 were in the CSF group (n = 54). 25-Hydroxy vitamin D levels were similar in both groups: 17.5 [3.3-36.1] ng/ml in the CSF group and 15.2 [5.3-34] ng/ml in the control group (P = 0.129). When we analyzed TFC for each of the coronary arteries, we found a weak negative correlation between vitamin D level and TFC of the right coronary artery in the CSF group (r = -0.314, P = 0.021). Parathyroid hormone levels were similar in both groups: 48 [16-140] pg/ml in the CSF group and 52 [25-125] pg/ml in the control group (P = 0.297). Conclusion: The study failed to demonstrate a relationship between serum parathyroid hormone level and CSF. However, a weak negative correlation was found between vitamin D level and TFC of the right coronary artery.


Assuntos
Circulação Coronária/fisiologia , Vasos Coronários/diagnóstico por imagem , Fenômeno de não Refluxo , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/diagnóstico , Vitamina D/análogos & derivados , Idoso , Calcifediol/sangue , Cálcio/sangue , Angiografia Coronária , Vasos Coronários/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio , Fósforo/sangue , Vitamina D/sangue , Deficiência de Vitamina D/sangue
19.
Eur J Endocrinol ; 181(5): 509-517, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31484162

RESUMO

Introduction: The role of vitamin D on bone microarchitecture and fragility is not clear. Objective: To investigate whether vitamin D deficiency (25(OH)D <20 ng/mL) increases cortical bone loss and the severity of fractures. Design: Cross-sectional study of 287 elderly women with at least one prevalent low-impact fracture. Methods: Biochemistry, X-rays to identify vertebral fractures (VFs) and to confirm non-vertebral fractures (NonVFs), and high-resolution peripheral quantitative computed tomography (HR-pQCT) to evaluate bone microstructure. Results: Serum 25(OH)D levels were associated with body mass index (BMI: r = -0.161, P = 0.006), PTH (r = -0.165; P = 0.005), CTX (r = -0.119; P = 0.043) and vBMD at cortical bone (Dcomp: r = 0.132; P = 0.033) and entire bone (D100: r = 0.162 P = 0.009) at the distal radius, but not at the tibia. Age and PTH levels were potential confounding variables, but in the multiple linear regressions only BMI (95% CI: 0.11-4.16; P < 0.01), 25(OH)D (95% CI: -0.007 to 1.70; P = 0.05) and CTX (95% CI: -149.04 to 21.80; P < 0.01) predicted Dcomp, while BMI (95% CI: 1.13-4.18; P < 0.01) and 25(OH)D (95% CI: 0.24-1.52; P < 0.01) predicted D100. NonVFs predominated in patients with 25(OH)D <20 ng/mL (P = 0.013). Logistic regression analysis showed a decrease in the likelihood of presenting grade 2-3 VFs/NonVFs for every increase in 25(OH)D (OR = 0.962, 95% CI: 0.940-0.984; P = 0.001), BMI (OR = 0.932, 95% CI: 0.885-0.981; P = 0.007) and D100 at radius (OR = 0.994, 95% CI: 0.990-0.998; P = 0.005). Conclusion: In elderly patients with prevalent fractures, vitamin D deficiency was associated with cortical bone loss and severity of fractures.


Assuntos
Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Osteoporose/epidemiologia , Osteoporose/etiologia , Deficiência de Vitamina D/complicações , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Hormônio Paratireóideo/sangue , Fraturas da Coluna Vertebral/epidemiologia , Fraturas da Coluna Vertebral/etiologia
20.
Prensa méd. argent ; 105(8): 431-435, sept 2019. graf
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1023142

RESUMO

Introducción: La monitorización con hormona tiroidea intraoperatoria (IOPTH) es utilizada en la práctica médica para predecir la cura bioquímica durante la paratiroidectomía del hiperparatiroidismo primario. Sin embargo, existen diversos criterios utilizados para predecir la normocalcémica luego de una paratiroidectomía. El propósito de este estudio es determinar cuál criterio es aquel que se corresponde con el menor riesgo de presentar un hiperparatiroidismo persistente luego de una paratiroidectomía por hiperparatiroidismo primario. Material y métodos: Se han analizado publicaciones realizadas en los últimos 10 años tomando como fuente de recopilación la base de datos de Pub-Med, trabajos publicados en Journal of the American Medical Associatiion y World Journal of Surgery. Conclusión: El criterio de IOPTH final en valores por debajo de los 65 pg/mL, y en especial, por debajo de los 40 pg/mL parece comportarse como mejor predictor de bajo riesgo de enfermedad persistente en comparación con el criterio de disminución de IOPTH por debajo del 50% del valor basal (AU)


Introduction: Monitoring with intraoperative thyroid hormone (IOPTH) is used in medical practice to predict the biochemical cure during the parathyroidectomy of primary hyperparathyroidism. However, there are several criteria used to predict normocalcemia after a parathyroidectomy. The purpose of this study is to determine which criterion is the one that correspons to the lowest risk of presenting a persistent hyperparathyroidism after a parathyroidectomy due to primary hyperparathyroidism. Materials and methods: Publications made in the last 10 years have been analyzed taking as a source of compilations the PubMed database, works published in Journal of the American Medical Association and World Journal of Surgery. Conclusiion: The final IOPTH criterion in values below 65 pg/mL, and especially below 40 pg/mL, seems to be the best predictor of low risk of persistent disease compared to the IOPTH decrease criterior Below 50% of the basal value (AU)


Assuntos
Humanos , Hormônio Paratireóideo , Neoplasias das Paratireoides/cirurgia , Medição de Risco , Hiperparatireoidismo Primário/cirurgia , Estudos de Viabilidade
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