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1.
J Endocrinol Invest ; 41(10): 1221-1226, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29516386

RESUMO

PURPOSE: To evaluate adherence to European Society of Endocrinology guidelines and risk of renal complications in patients with chronic post-operative hypoparathyroidism (PO-HypoPT) treated with calcium and activated vitamin D metabolites. METHODS: We evaluated 90 adult patients (68 females and 22 males) with chronic (3 years) PO-HypoPT. Total albumin-corrected (Alb-Ca) and ionized serum calcium, phosphate, creatinine, PTH, and 24-h urinary calcium were measured; renal ultrasound was also performed. Healthy hospital employers (n = 142) were used as control. RESULTS: Complete data were available in 82 patients. Twenty-eight (34.1%) met four targets (Alb-Ca, phosphate, calcium phosphate product and 24-h urinary calcium), 36 (43.9%) three, 17 (20.7%) two, and 1 (1.2%) one. Thirteen (14.4%) had Alb-Ca value below and 18 (20.0%) above the target range and 54.9% 24-h urinary calcium above the upper normal limit. Seven (7.7%) has increased serum phosphate and none an increased calcium phosphate product. Eleven (12.2%) patients had eGFR < 60 mL/min × 1.73 m2. Nephrolithiasis was present in 27 (30%) patients. Compared with the controls, patients had lower Alb-Ca (8.9 ± 0.5 vs. 9.5 ± 0.3 mg/dL, P 0.0001) and a higher rate of kidney stones, mostly asymptomatic [27/90 (30%) vs 7/142 (5%), P < 0.0001, odd ratio 8.2 (3.4-19.9)]. Fifty-seven patients had ≥ four serum Ca2+ determinations during follow-up. Forty (70.2) patients had values within the target range in > 50% of cases, 18 in > 75%, and only 2 in 100%. Two patients never had values in the target range. CONCLUSIONS: Treatment of chronic PO-HypoPT with calcium and activated vitamin D metabolites is suboptimal and associated with an increased risk of renal complications.


Assuntos
Gerenciamento Clínico , Hipoparatireoidismo/sangue , Hipoparatireoidismo/tratamento farmacológico , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Idoso , Cálcio/efeitos adversos , Cálcio/uso terapêutico , Doença Crônica , Estudos de Coortes , Feminino , Seguimentos , Humanos , Hipoparatireoidismo/diagnóstico , Nefropatias/sangue , Nefropatias/induzido quimicamente , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Vitamina D/efeitos adversos , Vitamina D/metabolismo , Vitamina D/uso terapêutico
2.
J Endocrinol Invest ; 39(7): 807-34, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26969462

RESUMO

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Conservadores da Densidade Óssea/uso terapêutico , Consenso , Endocrinologistas , Feminino , Humanos , Itália , Masculino
3.
J Endocrinol Invest ; 35(7): 655-60, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21971564

RESUMO

BACKGROUND: Patients with primary hyperparathyroidism (PHPT) with contraindications to parathyroidectomy (PTx) or persistent PHPT have few non surgical options. AIM: The aim of the study was to investigate the efficacy of cinacalcet in reducing serum calcium in patients with PHPT, for whom PTx would be indicated according to serum calcium levels, but in whom PTx is not clinically appropriate or is contraindicated [European Medicines Agency (EMA) prescription labeling]. SUBJECTS AND METHODS: The study (open-label prospective, conducted in a single tertiary center) included 12 sporadic and 2 multiple endocrine neoplasia type 1 PHPT patients with serum calcium greater than 11.2 mg/dl. Cinacalcet was administered in increasing doses until normal serum calcium was reached or side effects preventing a further increase occurred. Serum calcium, PTH, phosphate, 25OHD, markers of bone turnover, 24h-urinary calcium and areal bone mineral density (BMD) were measured. Safety biochemical indices and adverse events were monitored. RESULTS: The maintenance cinacalcet dose [median 30 mg twice daily (range 30 daily-60 mg twice daily)] was maintained constant during follow-up (median 12 months). Mean±SE baseline serum calcium was 12.2±0.3 mg/dl. Serum calcium decreased by at least 1 mg/dl in all patients and normalized in 10. Serum calcium at the last observation was 9.9±0.2 mg/dl (p<0.0001 vs baseline). PTH decreased by 17.1% compared to baseline (p=0.13), and never reached a normal value. BMD was unchanged. Adverse events occurred in 6 patients (43%) and required treatment withdrawal in 2. CONCLUSIONS: Cinacalcet reduced and often normalized serum calcium in PHPT patients who met the EMA labeling.


Assuntos
Hipercalcemia/prevenção & controle , Hiperparatireoidismo Primário/tratamento farmacológico , Moduladores de Transporte de Membrana/uso terapêutico , Naftalenos/uso terapêutico , Receptores de Detecção de Cálcio/agonistas , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cinacalcete , Contraindicações , Rotulagem de Medicamentos , União Europeia , Feminino , Seguimentos , Humanos , Hipercalcemia/etiologia , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/fisiopatologia , Quimioterapia de Manutenção , Moduladores de Transporte de Membrana/efeitos adversos , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/fisiopatologia , Naftalenos/efeitos adversos , Paratireoidectomia , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Índice de Gravidade de Doença
4.
J Mech Behav Biomed Mater ; 115: 104294, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33383376

RESUMO

The valve replacement therapy is the standard treatment for severe heart valve diseases. Nowadays, two types of commercial prosthesis are available: mechanical and biological, but both of them have severe limitations. Moreover, alternative therapeutic approach for valve replacement, based on minimally invasive techniques (MIAVR), motivates the search for new valve materials. In this study a polyurethane-based self-expandable tri-leaflets heart valve compatible with MIAVR procedure is proposed. The device is based on the development, fabrication and characterization of three different elements: the leaflets, the polymeric stent for supporting the leaflets, and the external metallic stent for anchoring the valve to the native aortic root. The polymeric stent and the valve leaflets were fabricated using a thermoplastic silicone-polycarbonate-urethane using 3D printing and spray technology while the external metallic stent was made in nickel titanium (Nitinol) to obtain a self-expandable valve after the crimping process. The three elements were assembled in the completed device and tested by crimping, fatigue and fluid-dynamic test. The novel polymeric valve proposed showed promising results about valve crimping capabilities, durability and fluid dynamic performances. This approach could offer advantages such as low cost and to produce a tailor-made device basing on patient's imaging data. Moreover, the selected biomaterial offers the potential to have a device that could need of permanent anticoagulation and lack of calcification.


Assuntos
Doenças das Valvas Cardíacas , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Valva Aórtica , Humanos , Desenho de Prótese , Stents
5.
Cardiovasc Eng Technol ; 11(5): 532-543, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748364

RESUMO

PURPOSE: Computational models of cardiovascular structures rely on their accurate mechanical characterization. A validated method able to infer the material properties of patient-specific large vessels is currently lacking. The aim of the present study is to present a technique starting from the flow-area (QA) method to retrieve basic material properties from magnetic resonance (MR) imaging. METHODS: The proposed method was developed and tested, first, in silico and then in vitro. In silico, fluid-structure interaction (FSI) simulations of flow within a deformable pipe were run with varying elastic modules (E) between 0.5 and 32 MPa. The proposed QA-based formulation was assessed and modified based on the FSI results to retrieve E values. In vitro, a compliant phantom connected to a mock circulatory system was tested within MR scanning. Images of the phantom were acquired and post-processed according to the modified formulation to infer E of the phantom. Results of in vitro imaging assessment were verified against standard tensile test. RESULTS: In silico results from FSI simulations were used to derive the correction factor to the original formulation based on the geometrical and material characteristics. In vitro, the modified QA-based equation estimated an average E = 0.51 MPa, 2% different from the E derived from tensile tests (i.e. E = 0.50 MPa). CONCLUSION: This study presented promising results of an indirect and non-invasive method to establish elastic properties from solely MR images data, suggesting a potential image-based mechanical characterization of large blood vessels.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Modelos Cardiovasculares , Modelagem Computacional Específica para o Paciente , Módulo de Elasticidade , Humanos , Imageamento por Ressonância Magnética/instrumentação , Imagens de Fantasmas , Valor Preditivo dos Testes , Impressão Tridimensional , Estudo de Prova de Conceito , Reprodutibilidade dos Testes , Resistência à Tração
6.
J Endocrinol Invest ; 30(6 Suppl): 8-12, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17721067

RESUMO

Cholesterol (C27H46O) is the principal structural lipid of the biological membrane, but it also plays an important role in many other biological functions. Even though the majority of body cholesterol is synthesized by the liver and secreted as circulating lipoproteins, many cell types can synthesize cholesterol ex novo. The biosynthetic pathway of cholesterol proceeds through several intermediates and involves different enzymes. The rate-limiting step of cholesterol synthesis is the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase that synthesizes mevalonate starting from HMG-CoA. Since natural inhibitors of HMG-CoA reductase, named statin, have been isolated, many others have been developed, which differ in their lipophilicity/ hydrophilicity. By using statins, many studies have been performed in order to shed light on the role of cholesterol on different cell types and, among these, on bone cells. In vivo studies have demonstrated that treatment of pluripotent mouse marrow stromal cells (M2-10B4) with statins inhibited the differentiation of these cells into osteoblastic cells, confirming the crucial role of cholesterol biosynthetic pathway for osteoblast differentiation. Conversely, other studies, using other cellular systems, have reported that statins may exert an anabolic effect on bone. Moreover, human and animal studies have shown that hypercholesterolemia may play an adverse effect in osteoporotic bone loss. In conclusion, it appears that cholesterol is important for different cellular activities, such as osteoblastic differentiation, if present in "normal" physiological concentration and particular experimental conditions, but it may exert adverse effects if present in excess.


Assuntos
Diferenciação Celular/fisiologia , Colesterol/biossíntese , Osteoblastos/fisiologia , Acil Coenzima A/metabolismo , Animais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Estrutura Molecular , Osteoblastos/citologia , Osteogênese/fisiologia
7.
J Endocrinol Invest ; 30(8): 666-71, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17923798

RESUMO

INTRODUCTION: An evaluation of PTH levels during thyroid surgery may reflect the functional status of the parathyroids and be useful in identifying patients at risk for hypocalcemia. This study aims to monitor the parathyroid function during total thyroidectomy through intra-operative serial samples for calcium and PTH. MATERIALS AND METHODS: Forty-seven patients undergoing total thyroidectomy for different diseases were selected for the study. Patients underwent serum PTH and calcium sampling at the induction of anesthesia (T0) and after the first (T1) and the second (T2) lobectomy. Serum calcium was also drafted 24 h after the operation. RESULTS: Mean PTH at T0, T1, and T2 was, respectively: 32.1 pg/ml, 19.6 pg/ml, and 11.5 pg/ml. PTH was significantly higher at T0 when compared to T1 (p<0.0001). It was also significantly higher at T1 than at T2 (p<0.0001). At T1 PTH levels were below the normal range in 20/47 cases (42.5%) and at T2 in 31/47 cases (66%). Twenty-four h after surgery, 8 patients (17%) demonstrated a biochemical hypocalcemia. A PTH value at T0 in the upper (>70 pg/ml) or in the lower (<20 pg/ml) limits of the normal range was statistically related to post-operative hypocalcemia (p=0.017). DISCUSSION: The study seems to confirm that serum PTH during thyroidectomy does not represent a sensitive tool in precociously identifying hypocalcemic patients. Nevertheless, before surgery, a PTH concentration at the higher or lower normal limit may help to identify patients "at risk" of developing hypocalcemia.


Assuntos
Hipocalcemia/epidemiologia , Glândulas Paratireoides/fisiologia , Hormônio Paratireóideo/sangue , Complicações Pós-Operatórias/epidemiologia , Tireoidectomia , Adolescente , Adulto , Idoso , Biomarcadores , Cálcio/sangue , Feminino , Humanos , Hipocalcemia/sangue , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Fatores de Risco
8.
Endocr Connect ; 4(3): 172-8, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26155986

RESUMO

We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30 ng/ml, estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m(2) and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD ≥30 ng/ml and eGFR ≥60 ml/min per 1.73 m(2) and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion.

9.
J Bone Miner Res ; 12(1): 72-7, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9240728

RESUMO

We measured bone mineral density (BMD) (lumbar spine, femoral neck, Ward's triangle, and trochanter) in 34 men given suppressive doses of levothyroxine (L-T4) for a mean of 10.2 years. Indications for treatment were nontoxic goiter (n = 5) or thyroidectomy for differentiated thyroid cancer (n = 6) or nontoxic goiter (n = 3). Patients were followed at our institution and treated with the minimal amount of L-T4 able to suppress thyroid-stimulating hormone (TSH). At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 14 men (41.2%). The mean daily dose of L-T4 was 172 +/- 6 microg, and the cumulative dose of L-T4 was 673 +/- 71 mg. We found no significant difference between patients and age- and weight-matched controls in BMD (g/cm2) at any site of measurement (lumbar spine 1.144 +/- 0.12 vs. 1.168 +/- 0.15; femoral neck 0.979 +/- 0.13 vs. 1.001 +/- 0.13; Ward's triangle 0.854 +/- 0.17 vs. 0.887 +/- 0.15; and trocanther 0.852 +/- 0.13 vs. 0.861 +/- 0.13). BMD was not correlated with the duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, osteocalcin, and bone alkaline phosphatase. Serum calcium and osteocalcin were slightly but significantly elevated in patients compared with controls, whereas there was no difference in intact parathyroid hormone, bone alkaline phosphatase, and sex hormone-binding globulin (marker of thyroid hormone action). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion, has no significant effects on bone metabolism and bone mass in men.


Assuntos
Densidade Óssea/efeitos dos fármacos , Tireotropina/antagonistas & inibidores , Tiroxina/efeitos adversos , Absorciometria de Fóton , Adulto , Fosfatase Alcalina/metabolismo , Fêmur/efeitos dos fármacos , Fêmur/fisiologia , Colo do Fêmur/efeitos dos fármacos , Colo do Fêmur/fisiologia , Bócio/tratamento farmacológico , Bócio/cirurgia , Humanos , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiologia , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Radioimunoensaio , Globulina de Ligação a Hormônio Sexual/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/efeitos adversos , Tiroxina/administração & dosagem , Tiroxina/sangue , Tiroxina/uso terapêutico , Tri-Iodotironina/sangue
10.
J Bone Miner Res ; 14(6): 878-82, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10352095

RESUMO

Inactivating mutations of the calcium-sensing receptor gene (CaR) might explain abnormalities in the regulation of both parathyroid cell proliferation and parathyroid hormone secretion. In a previous study, using RNAse A protection assay, no mutations were identified in a series of parathyroid specimens from patients with primary and secondary hyperparathyroidism, but the analysis was incomplete, since part of exon 6 could not be analyzed. In the present study, we examined the presence of mutations in the CaR gene in 20 parathyroid adenomas using direct sequencing. The entire coding region of the CaR gene was successfully amplified by polymerase chain reaction and directly sequenced. This analysis did not identify CaR gene mutations in any tumors studied. A polymorphism that encoded a single amino acid change (Ala826Thr) was identified in 4 parathyroid adenomas and in 8 of 50 normal unrelated subjects. Loss of heterozygosity studies were also performed on adenomas using markers for the locus of the CaR gene on chromosome 3q. No allelic loss was demonstrated. In conclusion, our results extend previous observation and suggest that clonal somatic mutations of the CaR gene and allelic loss at the CaR locus on chromosome 3q do not play a major role in the pathogenesis of sporadic parathyroid tumors.


Assuntos
Adenoma/genética , Cálcio/metabolismo , Neoplasias das Paratireoides/genética , Periodicidade , Receptores de Superfície Celular/genética , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Receptores de Detecção de Cálcio
11.
Hum Mutat ; 16(5): 445, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11058905

RESUMO

We report nine mutations of the multiple endocrine neoplasia type 1 (MEN1) gene in sporadic parathyroid adenomas. Six of them have not previously been described: E60X, P32R, 261delA, 934+2T-->G, S443P, and 1593insC. The tissue samples were initially submitted to LOH analysis at 11q13 followed by SSCP screening of LOH-positive samples. Mutations were identified by direct sequencing and subcloning. Three (E60X, P32R, and 261delA) were in exon 2, one (934+2bp) in the splice junction of exon 5, one (S443P) in exon 9, and one (1593insC) in exon 10. The 3 mutations in exon 2 were associated with loss and/or creation of a restriction site. The corresponding germline sequence of the MEN1 gene was normal. Most mutations would likely result in a nonfunctional menin protein, and therefore in the loss of a tumor suppressor protein.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação/genética , Neoplasias das Paratireoides/genética , Proteínas Proto-Oncogênicas , Adenoma/genética , Idoso , Genes Supressores de Tumor/genética , Humanos , Masculino , Mutagênese Insercional/genética , Mutação de Sentido Incorreto/genética , Proteínas de Neoplasias/genética , Deleção de Sequência/genética
12.
J Clin Endocrinol Metab ; 78(4): 818-23, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8157704

RESUMO

We measured total body and regional (lumbar spine, femoral neck, Ward's triangle, and trochanter) bone mineral density (BMD) in 47 premenopausal women chronically treated with suppressive doses of levothyroxine (L-T4). Treatment was administered to 7 patients with nontoxic goiter or, after thyroidectomy, to 38 patients with differentiated thyroid cancer and 2 with nontoxic goiter. Patients were followed at our institution and treated with the minimal amount of L-T4 necessary to suppress TSH. At the time of evaluation, free T3 was normal in all cases, whereas free T4 was increased in 17 (36.2%). The mean daily dose of L-T4 was 154.3 +/- 5 micrograms, and the mean duration of treatment was 10.1 yr. We found no significant difference between patients and age- and weight-matched controls in BMD at any site of measurement. BMD was not correlated with duration of therapy, cumulative or mean daily dose of L-T4, serum levels of free T4, free T3, and osteocalcin. There was no difference between patients and controls in serum total calcium, intact PTH, osteocalcin, or carboxy-terminal cross-linked telopeptide of type I collagen or in the concentrations of two markers of thyroid hormone action (sex hormone-binding globulin and amino-terminal propeptide of type III procollagen). Our data suggest that L-T4 suppressive therapy, if carefully carried out and monitored, using the smallest dose necessary to suppress TSH secretion has no significant effect on bone metabolism or bone mass.


Assuntos
Osteoporose/induzido quimicamente , Pré-Menopausa/fisiologia , Tireotropina/antagonistas & inibidores , Tiroxina/efeitos adversos , Tiroxina/uso terapêutico , Adulto , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Relação Dose-Resposta a Droga , Feminino , Bócio/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Osteocalcina/sangue , Osteoporose/sangue , Hormônio Paratireóideo/sangue , Pré-Menopausa/sangue , Pró-Colágeno/sangue , Globulina de Ligação a Hormônio Sexual/análise , Neoplasias da Glândula Tireoide/tratamento farmacológico , Tiroxina/sangue , Tiroxina/metabolismo , Fatores de Tempo , Tri-Iodotironina/sangue , Tri-Iodotironina/metabolismo
13.
J Clin Endocrinol Metab ; 85(12): 4789-94, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11134144

RESUMO

A reduced expression of calcium-sensing receptor (CaR) messenger ribonucleic acid and protein accompanied by abnormalities in parathyroid cell proliferation and PTH secretion are present in primary hyperparathyroidism. We studied the expression of CaR protein by immunohistochemistry in 36 sporadic parathyroid adenomas and investigated the relationship between CaR expression and several preoperative clinical parameters, including the set-point of Ca(2+)-regulated PTH secretion (measured in vivo). The adenomas were classified in 4 categories according to the intensity of immunohistochemical staining: 5 (14%) showed a CaR staining intensity similar to that of normal parathyroid ( ), 10 (27%) showed moderate staining (++), 16 (45%) showed weak staining (+), and 5 (14%) were negative (-). The intensity of CaR staining was not related to preoperative serum Ca(2+), PTH levels or adenoma volume. Twenty-nine patients underwent preoperatively the calcium infusion test to evaluate the PTH-Ca(2+) set-point. Individual values of PTH-Ca(2+) set-point ranged from 1.38-1.93 mmol/L and were significantly correlated with basal Ca(2+) levels (r = 0.96; P: = 0. 0001) and adenoma volume (r = 0.5; P: = 0.01). The mean PTH-Ca(2+) set-point values were significantly different in the 4 groups of patients classified according to immunohistochemical staining intensity of their adenoma (P: = 0.025; F = 3.78); the mean PTH-Ca(2+) set-point was significantly higher in the groups classified as negative than in those classified as weak or moderate. No correlation was observed between the PTH-Ca(2+) set-point and basal PTH levels or between the percent maximal PTH inhibition and adenoma volume and basal PTH or Ca(2+) levels. In summary, our data suggest that there is a relationship between apparent CaR protein expression and PTH-Ca(2+) set-point abnormality, suggesting that a reduced receptor content might have an important role in the pathogenesis of primary hyperparathyroidism.


Assuntos
Cálcio/metabolismo , Hiperparatireoidismo/metabolismo , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismo , Receptores de Superfície Celular/biossíntese , Adenoma/metabolismo , Adulto , Idoso , Western Blotting , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/metabolismo , Receptores de Detecção de Cálcio
14.
Mol Cell Endocrinol ; 161(1-2): 47-51, 2000 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-10773391

RESUMO

We investigated 22 male patients affected by prepubertal hypogonadism with a mean age of 34.3+/-5.2. A significant reduction of bone mineral density (BMD) at both the lumbar spine (L2-L4, -14%, 1.039+/-0.11 vs. 1.217+/-0.16 g/cm(2), P=0.005) and femoral neck (-11%; 0.927+/-0.09 vs. 1.034+/-0.16 g/cm(2), P=0.01) was found in patients compared to age-matched controls. The mean Z score was -1. 55 for vertebrae and -1.33 for femur. Eleven and nine patients, respectively, had a lumbar and femoral BMD at least 1 S.D. below the normal mean; 8 and 4, respectively, 2 S.D. below. There was a strong positive correlation between BMD and duration of hormone replacement treatment (HRT) for both sites: respectively, r=0.71, P<0.005 for the vertebrae, and r=0.60, P<0.01 for the femur. A weak correlation was also present between onset of HRT and BMD: r=0.6, P<0.01 at the lumbar level, and r=0.47, P<0.05 at the femoral neck.


Assuntos
Densidade Óssea/efeitos dos fármacos , Terapia de Reposição Hormonal , Hipogonadismo/metabolismo , Adulto , Idade de Início , Remodelação Óssea/efeitos dos fármacos , Estudos de Casos e Controles , Colo do Fêmur , Humanos , Hipogonadismo/congênito , Hipogonadismo/tratamento farmacológico , Modelos Lineares , Região Lombossacral , Masculino , Análise por Pareamento , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/urina
15.
Eur J Endocrinol ; 140(5): 429-33, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10229909

RESUMO

OBJECTIVE: To report a new mutation of the multiple endocrine neoplasia type 1 (MEN1) gene in an Italian kindred. DESIGN: The study included the female proband, aged 50 years, affected by primary hyperparathyroidism, insulinoma and prolactinoma, and ten relatives. Blood samples were obtained for biochemical and genetic analyses. Clinical screening tests included serum glucose, ionized calcium, intact parathyroid hormone, GH, insulin and prolactin. The coding sequence, including nine coding exons and 16 splice sites, was amplified by PCR and directly sequenced. RESULTS: Two additional cases of primary hyperparathyroidism were identified among the paternal family members. The sequence analysis showed a heterozygous T to C transition at codon 444 in exon 9, resulting in a leucine to proline substitution (L444P) in the patient and in the two paternal family members with primary hyperparathyroidism. The L444P amino acid change was absent in 50 normal subjects. The mutation determined the loss of a BlnI restriction site of the wild-type sequence and the creation of a new restriction EcoRII site. The patient, but not her paternal affected relatives, also had a common heterozygous polymorphism (D418D) in exon 9. CONCLUSIONS: A new MEN1 mutation (L444P) in exon 9 has been identified; this substitution caused the loss of a BlnI restriction site and the creation of a new EcoRII site.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1/genética , Mutação/fisiologia , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas , Elementos Antissenso (Genética) , Códon/genética , Éxons/genética , Feminino , Humanos , Leucina/metabolismo , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Polimorfismo de Fragmento de Restrição , Prolina/metabolismo
16.
Eur J Endocrinol ; 148(6): 603-7, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12773131

RESUMO

OBJECTIVE: Calcium-sensing receptor (CaR) is a candidate gene for osteoporosis susceptibility. Several CaR polymorphisms have been identified and an association between the A986S genotype and serum calcium levels has been found in Canadian postmenopausal women. We investigated whether the presence of 986S allele was associated with bone mineral density (BMD) and osteoporotic fractures. DESIGN: The study group consisted of 164 Italian postmenopausal women without fragility fracture (Fx(-)) and 55 women with fracture (Fx(+)). METHODS: A fragment of exon 7 of CaR gene containing three polymorphisms (A986S, R990G and Q1011E) was amplified by PCR and sequenced. Anthropometric characteristics and BMD were evaluated. RESULTS: The A986S polymorphism was the most commonly observed (27.9%), whereas the other two CaR polymorphisms, R990G and Q1011E, occurred in a minority of cases (8.8 and 5.5% respectively). There was no significant difference in the frequency distribution of any CaR allele between Fx(-) and Fx(+) patients. Body mass index was found to predict BMD at the lumbar spine and femoral neck. The A986S polymorphism and Years since menopause were not independent predictors of BMD at any site. As far as fracture occurrence, there was no statistically significant difference in the prevalence of fractures between women carrying or not carrying the 986S allele. CONCLUSIONS: Our data do not support a role of A986S CaR polymorphism in BMD and in the prevalence of fragility fractures in Italian postmenopausal women.


Assuntos
Densidade Óssea/genética , Fraturas Espontâneas/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo Genético , Receptores de Superfície Celular/genética , Idoso , Feminino , Fraturas Espontâneas/epidemiologia , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Itália , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/epidemiologia , Pós-Menopausa , Valor Preditivo dos Testes , Prevalência , Receptores de Detecção de Cálcio
17.
Eur J Endocrinol ; 146(6): 783-8, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12039698

RESUMO

OBJECTIVE: The traditional surgical approach for patients with primary hyperparathyroidism (PHPT) consists of the identification of at least four glands and in the removal of all hyperfunctioning parathyroid tissue. DESIGN: To evaluate whether intraoperative parathyroid hormone (PTH) monitoring will allow a more limited surgical procedure by confirming complete removal of all hyperfunctioning tissue. METHODS: Plasma samples were obtained from 206 consecutive patients with sporadic PHPT before skin incision, during manipulation of a suspected adenoma, and 5 min (T-5) and 10 min after removal of abnormal parathyroid tissue. PTH was measured by a quick immunochemiluminescent assay (QPTH). The operative success was defined by a decrease of PTH greater than 50% of the highest pre-excision value. RESULTS: A >50% decrease of PTH occurred in 203 patients and was evident at T-5 in the majority of cases. All but three had normal serum calcium the day after surgery and afterwards. PTH concentration did not show a >50% decrease in the remaining three cases after completion of surgery. One patients had negative neck exploration and remained hypercalcemic; the other two had normal serum calcium at follow-up. Thus, the intraoperative QPTH correctly predicted the outcome of surgery in 201 patients (97.5%) (200 true positive and 1 true negative), and provided three false positive and two false negative results. CONCLUSIONS: The intraoperative QPTH measurement represents a useful tool to assist the surgeon during parathyroidectomy. It indicates whether all hyperfunctioning parathyroid tissue has been removed, limiting the procedure to a unilateral neck exploration in most cases.


Assuntos
Hiperparatireoidismo/sangue , Hiperparatireoidismo/cirurgia , Hormônio Paratireóideo/sangue , Paratireoidectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória
18.
Eur J Endocrinol ; 139(1): 72-7, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9703381

RESUMO

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.


Assuntos
Adenoma/metabolismo , Adenoma/patologia , Biópsia por Agulha , Hormônio Paratireóideo/metabolismo , Neoplasias das Paratireoides/metabolismo , Neoplasias das Paratireoides/patologia , Adenoma/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico , Cintilografia , Ultrassonografia
19.
Surgery ; 124(6): 1077-9; discussion 1079-80, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9854586

RESUMO

BACKGROUND: Preoperative localization of parathyroid lesions and intraoperative quick parathyroid hormone (PTH) assay have been proposed to minimize the extent of operation in primary hyperparathyroidism. To this purpose, endoscopic procedures have been introduced recently. METHODS: During a period of 13 months, 39 of 65 consecutive patients with primary hyperparathyroidism were selected for endoscopic parathyroidectomy on the basis of the following criteria: preoperative echographic diagnosis of a single adenoma, absence of nodular goiter, and no prior neck operations. Unilateral neck exploration and excision of the adenoma was performed through a gasless procedure combined with intraoperative PTH measurements. Mean follow-up after the operation was 7 months (range 1 to 13 months). RESULTS: Thirty-nine parathyroid adenomas were removed; the mean diameter was 21 mm (range 5 to 30 mm). The mean operative time was 65 minutes (range 30 to 180 minutes). In all cases PTH concentration decreased significantly. Patients who underwent endoscopic parathyroidectomy had less postoperative pain compared with patients who underwent conventional hemithyroidectomy. At follow-up, serum calcium and PTH levels were normal in all cases. CONCLUSIONS: Endoscopic parathyroidectomy proved to be a feasible surgical procedure that can be performed in an acceptable operative time with an excellent cosmetic result. The gasless approach avoided any emphysema.


Assuntos
Endoscopia , Hiperparatireoidismo/cirurgia , Paratireoidectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade
20.
Surgery ; 126(6): 1117-21; discussion 1121-2, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10598196

RESUMO

BACKGROUND: Several studies demonstrated the feasibility of minimally invasive parathyroidectomy as a treatment for primary hyperparathyroidism. We compared its results with those of traditional surgery in a prospective randomized study. METHODS: From March to November 1998, 38 patients eligible for video-assisted parathyroidectomy (VAP) were referred to us. They were randomly divided into 2 groups: patients of group A underwent a conventional cervicotomy with bilateral exploration and frozen section of the removed adenoma; patients of group B underwent VAP with intraoperative measurement of parathyroid hormone. Operative time, postoperative pain, fever and hypocalcemia, cosmetic result, and costs were compared. Two cases of VAP were performed with locoregional anesthesia. RESULTS: Groups A (18 patients) and B (20 patients) were statistically balanced. Operative time was significantly shorter in group B (57 vs 70 minutes). Cosmetic result was significantly better in group B, which also experienced less postoperative pain (P < .05). No cases of persistent primary hyperparathyroidism were present in either group, but recurrent laryngeal nerve palsy occurred in 1 patient in group B. CONCLUSIONS: Compared with conventional surgery, VAP is associated with a shorter operative time, a better cosmetic result, and a less painful postoperative course.


Assuntos
Hiperparatireoidismo/cirurgia , Paratireoidectomia/economia , Paratireoidectomia/métodos , Cirurgia Vídeoassistida/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Custos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/economia , Pescoço/cirurgia , Medição da Dor , Dor Pós-Operatória , Paratireoidectomia/instrumentação , Satisfação do Paciente , Estudos Prospectivos , Resultado do Tratamento
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