Therapeutic Management and Long-Term Outcome of Hyperthyroidism in Patients with Antithyroid-Induced Agranulocytosis: A Retrospective, Multicenter Study.

BACKGROUND: Antithyroid drug-induced agranulocytosis (AIA) (neutrophils <500/µL) is a rare but serious complication in the treatment of hyperthyroidism. METHODOLOGY: Adult patients with AIA who were followed up at 12 hospitals in Spain were retrospectively studied. A total of 29 patients were studied. The etiology of hyperthyroidism was distributed as follows: Graves' disease (n = 21), amiodarone-induced thyrotoxicosis (n = 7), and hyperfunctioning multinodular goiter (n = 1). Twenty-one patients were treated with methimazole, as well as six patients with carbimazole and two patients with propylthiouracil. RESULTS: The median (IQR) time to development of agranulocytosis was 6.0 (4.0-11.5) weeks. The most common presenting sign was fever accompanied by odynophagia. All of the patients required admission, reverse isolation, and broad-spectrum antibiotics; moreover, G-CSF was administered to 26 patients (89.7%). Twenty-one patients received definitive treatment, thirteen patients received surgery, nine patients received radioiodine, and one of the patients required both treatments. Spontaneous normalization of thyroid hormone values occurred in six patients (four patients with amiodarone-induced thyrotoxicosis and two patients with Graves' disease), and two patients died of septic shock secondary to AIA. CONCLUSIONS: AIA is a potentially lethal complication that usually appears around 6 weeks after the initiation of antithyroid therapy. Multiple drugs are required to control hyperthyroidism before definitive treatment; additionally, in a significant percentage of patients (mainly in those treated with amiodarone), hyperthyroidism resolved spontaneously.

Efectos agudos y a largo plazo del tratamiento con zolendronato en pacientes adultos con osteogénesis imperfecta. Estudio español observacional con 5 años de seguimiento / Acute and long-term effects of zoledronate in adult patients with osteogenesis imperfecta. An observational Spanish study with five years of follow-up

La osteogénesis imperfecta (OI) es una enfermedad genética que cursa con baja densidad mineral y fragilidad ósea. Varios trabajos han demostrado la eficacia de los bisfosfonatos para mejorar la densidad mineral ósea (DMO). El objetivo de este estudio es evaluar la evolución de la DMO y parámetros bioquímicos de metabolismo óseo, en pacientes adultos con OI tratados con ácido zoledrónico intravenoso (iv) durante un periodo medio de 5 años, así como valorar la seguridad de dicho tratamiento. Pacientes y métodos: Estudio prospectivo, observacional en pacientes adultos con OI con osteoporosis u osteopenia, con T-score<-2, a los que se administró ácido zoledrónico (4mg iv) cada 6 meses durante 3 años y posteriormente de forma anual. Se registraron a las 24 y 48 h los cambios agudos en calcio, fósforo, creatinina y hemograma así como los efectos secundarios tras la infusión. Se realizó densitometría basal y cada año. Se determinaron basal y anualmente calcio, fósforo, paratohormona (PTHi), 25OH-vitamina D y marcadores de remodelado óseo (fosfatasa alcalina ósea, ß-cross-lap y deoxipiridolina en orina). Se registraron las nuevas fracturas. Resultados: Se trataron 20 pacientes, 6 hombres y 14 mujeres con una mediana de seguimiento de 5 años. Los niveles de calcio y las plaquetas disminuyeron significativamente a las 24 y 48 h tras la primera infusión. El recuento de hematíes disminuyó a las 24h. Estos cambios no fueron clínicamente relevantes. Siete pacientes presentaron un cuadro pseudogripal tras la primera dosis. La DMO medida en columna lumbar mostró un aumento significativo (6,7%) a los 12 meses de seguimiento (0,741±0,178 vs. 0,791±0,140g/cm2; p=0,003) así como a los tres (5,7%) y 5 años (9%) de seguimento. En cuello femoral se evidenció incremento significativo de la DMO a los 3 años (11,1%): 0,648±0,148 vs. 0,720±0,138g/cm2; p=0,01. En cadera total el incremento (10,1%) resultó significativo a los 3 años de tratamiento (0,706±0,118 vs. 0,720±0,138; p=0,01). No se evidenciaron diferencias significativas en los niveles de calcio y 25OH-vitamina D largo del seguimiento, el fósforo disminuyó significativamente al año y PTHi aumentó a los 3 años. ß-cross-lap disminuyó al año de tratamiento. Solo un paciente ha presentado nuevas fracturas. Conclusiones: El ácido zoledrónico es un tratamiento cómodo, seguro y eficaz para mejorar la DMO en pacientes adultos con OI

Osteogenesis imperfecta (OI) is an inherited disorder that causes low mineral density and bone fragility. Previous studies have shown the efficacy of bisphosphonates to increase bone mineral density (BMD). This study assessed changes over time in BMD and biochemical markers of bone metabolism in adult patients with osteogenesis imperfecta treated with intravenous zoledronic acid and the safety of this treatment. Patients and methods: A prospective, observational study in patients with OI, osteoporosis or osteopenia (T score <-2) who were administered zoledronic acid infusions (4mg IV) every 6 months for three years and annually thereafter. Densitometry was performed annually. Acute changes in complete blood count and calcium, phosphate, and creatinine levels, as well as side effects of the infusion, were recorded 24 and 48h after treatment. Calcium, phosphate, parathyroid hormone (iPTH), 25OH-vitamin D and bone turnover markers (bone alkaline phosphatase, ß-crosslaps and urinary deoxypyridinoline) were measured at baseline and every 12 months. Adverse events and new fractures were recorded. Results: Twenty patients (6 men and 14 women) were treated. Median follow-up time was five years. Calcium levels and platelet counts significantly decreased 24 and 48hours after the first infusion, and the red blood cell count decreased at 24hours. These changes were not clinically relevant. Seven patients experienced a flu-like episode after the first dose. Treatment induced significant increases in BMD in the lumbar spine (6.7%) after 12 months of follow-up (0.791±0.178 vs. 0.791±0.140g/cm2, p=.003) and at three (5.7%) and five years (9%) of follow-up. Femoral neck BMD significantly increased after 3 years (11.1%): 0.648±0.148 vs. 0.720±0.138g/cm2; p=.01. In total hip, increase in BMD (10.1%) was significant after three years of treatment (0.706±0.118 vs. 0.720±0.138, p=.01). There were no significant differences in calcium and 25OH-vitamin D levels during follow-up, phosphorus significantly decreased after one year, and iPTH increased at three years. ß-crosslaps decreased after one year of treatment. Only one patient sustained new fractures. Conclusions: Zoledronic acid is a convenient, safe, and effective treatment that increases BMD in adult patients with OI

Acute and long-term effects of zoledronate in adult patients with osteogenesis imperfecta. An observational Spanish study with five years of follow-up. / Efectos agudos y a largo plazo del tratamiento con zolendronato en pacientes adultos con osteogénesis imperfecta. Estudio español observacional con 5 años de seguimiento.

Osteogenesis imperfecta (OI) is an inherited disorder that causes low mineral density and bone fragility. Previous studies have shown the efficacy of bisphosphonates to increase bone mineral density (BMD). This study assessed changes over time in BMD and biochemical markers of bone metabolism in adult patients with osteogenesis imperfecta treated with intravenous zoledronic acid and the safety of this treatment. PATIENTS AND METHODS: A prospective, observational study in patients with OI, osteoporosis or osteopenia (T score <-2) who were administered zoledronic acid infusions (4mg IV) every 6 months for three years and annually thereafter. Densitometry was performed annually. Acute changes in complete blood count and calcium, phosphate, and creatinine levels, as well as side effects of the infusion, were recorded 24 and 48h after treatment. Calcium, phosphate, parathyroid hormone (iPTH), 25OH-vitamin D and bone turnover markers (bone alkaline phosphatase, ß-crosslaps and urinary deoxypyridinoline) were measured at baseline and every 12 months. Adverse events and new fractures were recorded. RESULTS: Twenty patients (6 men and 14 women) were treated. Median follow-up time was five years. Calcium levels and platelet counts significantly decreased 24 and 48hours after the first infusion, and the red blood cell count decreased at 24hours. These changes were not clinically relevant. Seven patients experienced a flu-like episode after the first dose. Treatment induced significant increases in BMD in the lumbar spine (6.7%) after 12 months of follow-up (0.791±0.178 vs. 0.791±0.140g/cm2, p=.003) and at three (5.7%) and five years (9%) of follow-up. Femoral neck BMD significantly increased after 3 years (11.1%): 0.648±0.148 vs. 0.720±0.138g/cm2; p=.01. In total hip, increase in BMD (10.1%) was significant after three years of treatment (0.706±0.118 vs. 0.720±0.138, p=.01). There were no significant differences in calcium and 25OH-vitamin D levels during follow-up, phosphorus significantly decreased after one year, and iPTH increased at three years. ß-crosslaps decreased after one year of treatment. Only one patient sustained new fractures. CONCLUSIONS: Zoledronic acid is a convenient, safe, and effective treatment that increases BMD in adult patients with OI.

Cambios estructurales y funcionales en el corazón de pacientes adultos con osteogénesis imperfecta: estudio de casos y controles / Structural and functional changes in the heart of adult patients with osteogenesis imperfecta: Case-control study

Introducción y objetivos: La osteogénesis imperfecta (OI) es una enfermedad del tejido conectivo que se caracteriza por una síntesis anómala del colágeno tipo i. Se sabe poco sobre la afectación cardiovascular que presentan estos pacientes. Las descritas con más frecuencia son la disfunción valvular y la dilatación de la aorta. Hemos querido analizar los cambios estructurales y funcionales del corazón en pacientes adultos con OI. Métodos: Estudiamos prospectivamente 82 pacientes con OI y los comparamos con 60 sujetos sanos emparejados por edad y sexo. A todos se les realizó un estudio ecocardiográfico. Resultados: No encontramos diferencias en la incidencia de valvulopatías respecto al grupo control. Nuestros pacientes tenían un mayor tamaño de la aurícula izquierda y mayores diámetros del ventrículo izquierdo (VI) ajustados por superficie corporal. La raíz de la aorta era significativamente mayor. La fracción de eyección del VI en los pacientes con OI era menor y tenían una presión sistólica de la arteria pulmonar mayor. Conclusiones: Los pacientes con OI presentan cambios estructurales y funcionales en el corazón. Sería recomendable un seguimiento para ver la evolución de estos cambios

Introduction and objectives: Osteogenesis imperfecta (OI) is a connective tissue disease characterised by an anomalous synthesis of type i collagen. Little is known about the cardiovascular affectation suffered by these patients. The most frequently described are valvular dysfunction and dilatation of the aorta. We wanted to analyse the structural and functional changes of the heart in adult patients with OI. Methods: We prospectively studied 82 patients with OI and compared them with 60 healthy subjects matched for age and sex. All of them underwent an echocardiographic study. Results: We found no differences in the incidence of valvulopathies compared to the control group. Our patients had a larger left atrium and larger left ventricle (LV) diameters adjusted for body surface area. Aortic root was significantly higher. LV ejection fraction in patients with OI was lower and they had higher pulmonary artery systolic pressure. Conclusions: Patients with OI suffer structural and functional changes in the heart. A follow-up is recommended to observe the evolution of these changes

Structural and functional changes in the heart of adult patients with osteogenesis imperfecta: Case-control study. / Cambios estructurales y funcionales en el corazón de pacientes adultos con osteogénesis imperfecta: estudio de casos y controles.

INTRODUCTION AND OBJECTIVES: Osteogenesis imperfecta (OI) is a connective tissue disease characterised by an anomalous synthesis of type i collagen. Little is known about the cardiovascular affectation suffered by these patients. The most frequently described are valvular dysfunction and dilatation of the aorta. We wanted to analyse the structural and functional changes of the heart in adult patients with OI. METHODS: We prospectively studied 82 patients with OI and compared them with 60 healthy subjects matched for age and sex. All of them underwent an echocardiographic study. RESULTS: We found no differences in the incidence of valvulopathies compared to the control group. Our patients had a larger left atrium and larger left ventricle (LV) diameters adjusted for body surface area. Aortic root was significantly higher. LV ejection fraction in patients with OI was lower and they had higher pulmonary artery systolic pressure. CONCLUSIONS: Patients with OI suffer structural and functional changes in the heart. A follow-up is recommended to observe the evolution of these changes.

Utilidad de la tomografía de emisión de positrones con 18F-fluorodesoxiglucosa en la evaluación prequirúrgica de masas adrenales con características radiológicas inespecíficas o sospechosas de malignidad en pacientes sin cáncer / Use of 18F-FDG-positron emission tomography in presurgical evaluation of nonspecific or suspectious adrenal masses in non-oncologic patients

Fundamento y objetivo: Valorar la utilidad de la 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET, «tomografía de emisión de positrones con 18F-fluorodesoxiglucosa») en la caracterización prequirúrgica de masas suprarrenales, en pacientes no oncológicos, cuyas características en TAC y/o RMN fueran inespecíficas o que presentaran alguna característica de malignidad. Pacientes y métodos: Estudio transversal y prospectivo en 12 pacientes con masa suprarrenal radiológicamente inespecífica o sospechosa de malignidad que iban a ser adrenalectomizados. Se realizó una 18F-FDG-PET calculándose la captación cuantitativa máxima de FDG (SUVmáx) en adrenal (SUVmáx adrenal) e hígado (SUVmáx hígado) y el cociente SUVmáx adrenal/hígado, que se relacionaron con el resultado anatomopatológico, evaluándose la fiabilidad de la prueba mediante receive operating curves (ROC, «curvas de rendimiento diagnóstico»). Resultados: Las curvas ROC para discriminar entre lesiones benignas y malignas mostraron que el SUVmáx era mejor parámetro que el tamaño o el cociente entre SUVmáx adrenal/hígado. Utilizando como punto de corte un valor de SUVmáx ≥ 3,1 los valores de sensibilidad, especificidad, valor predictivo positivo y negativo de la prueba fueron 100, 67, 50 y 100%, respectivamente, mientras que un cociente SUVmáx adrenal/hígado ≥ 1,8 mostró una sensibilidad, una especificidad, un valor predictivo positivo y un valor predictivo negativo de 67, 100, 100 y 90%, respectivamente. La presencia de un cociente SUVmáx adrenal/hígado ≥ 1,8 mostró una asociación estadísticamente significativa con la aparición de carcinoma. Conclusión: La 18F-FDG-PET puede ser de utilidad en la caracterización de masas suprarrenales inespecíficas o sospechosas, descubiertas en pacientes no oncológicos. Su uso en algunos casos podría evitar intervenciones innecesarias (AU)

Background and objective: Our purpose was to assess the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in pre-surgical characterization of adrenal masses. These masses were incidentally discovered in non-oncologic patients or during the study of endocrine hormone overproduction. These nodular lesions showed nonspecific or suspicious radiological features in the imaging tests routinely performed (CT and/or MRI). Patients and methods: This is a cross-sectional and prospective study in 12 patients with adrenal masses which were radiologically non-specific or suspicious for malignancy before adrenalectomy. An 18F-FDG-PET was made and quantitative FDG uptake (SUVmax) in the adrenal region (adrenal SUVmax) and liver (liver SUVmax), and the ratio SUVmax adrenal/liver was calculated. These parameters were related to the pathological findings. We evaluated the accuracy of the test by receive operating curves (ROC). Results: The ROC to discriminate between benign and malignant lesions showed that the SUVmax was a better parameter than size or SUVmax adrenal/liver ratio. Using a SUVmax cutoff value ≥ 3.1, sensitivity, specificity, positive and negative predictive value of the test were 100, 67, 50 and 100%, while a SUVmax adrenal/liver ratio ≥ 1.8 showed a sensitivity, specificity, positive and negative predictive value of 67, 100, 100 and 90%, respectively. The presence of a SUVmax adrenal/liver ratio ≥ 1.8 showed a statistically significant association with carcinoma occurrence. Conclusion: 18F-FDG-PET may be useful in the characterization of nonspecific or suspicious adrenal masses discovered in patients without a previous history of cancer. Its use in some cases could avoid unnecessary interventions (AU)

[Use of 18F-FDG-positron emission tomography in presurgical evaluation of nonspecific or suspectious adrenal masses in non-oncologic patients]. / Utilidad de la tomografía de emisión de positrones con 18F-fluorodesoxiglucosa en la evaluación prequirúrgica de masas adrenales con características radiológicas inespecíficas o sospechosas de malignidad en pacientes sin cáncer.

BACKGROUND AND OBJECTIVE: Our purpose was to assess the utility of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in pre-surgical characterization of adrenal masses. These masses were incidentally discovered in non-oncologic patients or during the study of endocrine hormone overproduction. These nodular lesions showed nonspecific or suspicious radiological features in the imaging tests routinely performed (CT and/or MRI). PATIENTS AND METHODS: This is a cross-sectional and prospective study in 12 patients with adrenal masses which were radiologically non-specific or suspicious for malignancy before adrenalectomy. An 18F-FDG-PET was made and quantitative FDG uptake (SUVmax) in the adrenal region (adrenal SUVmax) and liver (liver SUVmax), and the ratio SUVmax adrenal/liver was calculated. These parameters were related to the pathological findings. We evaluated the accuracy of the test by receive operating curves (ROC). RESULTS: The ROC to discriminate between benign and malignant lesions showed that the SUVmax was a better parameter than size or SUVmax adrenal/liver ratio. Using a SUVmax cutoff value≥3.1, sensitivity, specificity, positive and negative predictive value of the test were 100, 67, 50 and 100%, while a SUVmax adrenal/liver ratio≥1.8 showed a sensitivity, specificity, positive and negative predictive value of 67, 100, 100 and 90%, respectively. The presence of a SUVmax adrenal/liver ratio≥1.8 showed a statistically significant association with carcinoma occurrence. CONCLUSION: 18F-FDG-PET may be useful in the characterization of nonspecific or suspicious adrenal masses discovered in patients without a previous history of cancer. Its use in some cases could avoid unnecessary interventions.

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