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1.
N Engl J Med ; 382(4): 341-352, 2020 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-31971679

RESUMEN

BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Receptor IGF Tipo 1/antagonistas & inhibidores , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Diplopía/tratamiento farmacológico , Método Doble Ciego , Esquema de Medicación , Exoftalmia/tratamiento farmacológico , Oftalmopatía de Graves/diagnóstico por imagen , Humanos , Análisis de Intención de Tratar , Imagen por Resonancia Magnética , Persona de Mediana Edad , Órbita/diagnóstico por imagen , Receptor IGF Tipo 1/inmunología , Autoinforme
2.
Rev Endocr Metab Disord ; 24(6): 1011-1029, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37665480

RESUMEN

Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Deficiencia de Vitamina D , Humanos , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/epidemiología , Deficiencia de Vitamina D/etiología , Suplementos Dietéticos , Vitaminas/uso terapéutico
3.
Ophthalmology ; 129(4): 438-449, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34688699

RESUMEN

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.


Asunto(s)
Exoftalmia , Oftalmopatía de Graves , Anticuerpos Monoclonales Humanizados/uso terapéutico , Diplopía , Oftalmopatía de Graves/tratamiento farmacológico , Humanos
4.
J Sex Med ; 19(9): 1479-1487, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35811288

RESUMEN

BACKGROUND: The integrity of the neural pathways that link genital sensitive areas to the brain and the correlation with subjective sensations in transgender women with gender dysphoria after gender affirming surgery (GAS) have not been explored in detail and remain controversial, so far. AIM: To test with electrophysiology the integrity of the nervous paths after GAS, and to explore the relationship between genital sensitivity and self-perceived orgasmic intensity in transgender women after GAS. METHODS: Six patients who underwent GAS between 2016 and 2019 were enrolled in the study, and the evaluation of genital and pelvic neural pathways was performed. OUTCOMES: Genital sensory thresholds (at clitoral, vaginal, and anal sites) investigated by Somatosensory Evoked Potentials (SEP) and the intensity of orgasm (measured by a psychometric tool, the Orgasmometer) were combined to obtain an objective and subjective evaluation. RESULTS: SSEPs confirmed the integrity of the large diameter, dorsal column-lemniscus pathway subserving the genital area after GAS. Perceptual Threshold (PT) values were much lower at the neoclitoris compared to neovagina and anal sites. There was no correlation between Orgasmometer and SEP at anal and neovaginal level, while a trend was found at clitoral level. CLINICAL IMPLICATION: These findings could lead clinicians to a better understanding of postsurgical sexual life in transgender women in order to develop surgical techniques that could focus more on functional aspects of neovagina and neoclitoris. STRENGTHS & LIMITATIONS: Limitations: study very preliminary/exploratory; small number of patients; no long-term follow-up. Strengths: first assessment of sensory pelvic floor innervation in transgender women after GAS; use of objective methods; first attempt at correlating objectives findings to subjective experience of the sexual orgasm. CONCLUSIONS: Our evaluation showed that SSEPs is a good indicator of neural sensitivity, especially in neoclitoris, and that these measurements were consistent with the analysis of self-perceived orgasmic intensity. Canale D, Molinaro A, Marcocci C, et al. Genital Sensitivity and Perceived Orgasmic Intensity in Transgender Women With Gender Dysphoria After Gender-Affirming Surgery: A Pilot Study Comparing Pelvic Floor Evoked Somatosensory Potentials and Patient Subjective Experience. J Sex Med 2022;19:1479-1487.


Asunto(s)
Disforia de Género , Personas Transgénero , Clítoris , Femenino , Humanos , Orgasmo , Diafragma Pélvico , Proyectos Piloto
5.
Rev Endocr Metab Disord ; 22(4): 1201-1218, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34940947

RESUMEN

The 4th International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended. Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes. Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values.


Asunto(s)
COVID-19 , Deficiencia de Vitamina D , Colecalciferol , Humanos , SARS-CoV-2 , Vitamina D , Deficiencia de Vitamina D/tratamiento farmacológico
6.
Acta Haematol ; 144(3): 302-307, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32906140

RESUMEN

Hypercalcemia is a significant feature of patients with active multiple myeloma (MM) with extensive bone disease. Among the causes of non-neoplastic hypercalcemia, primary hyperparathyroidism (PHPT) is one of the most common, leading to osteoporosis and bone fractures. Interestingly, some preclinical data indicate that high secretion of parathyroid hormone (PTH) may have a negative impact on bone disease and MM progression. However, concomitant diagnosis of MM and PHPT has rarely been described. Here, we present 4 cases of patients with active MM and hypercalcemia with high or inappropriately normal PTH levels. Interestingly, CD138+ cells from these 4 MM patients lack PTH receptor 1 and PTH-related peptide expressions, indicating that PTH could have a paracrine rather than a direct pro-tumoral effect. Moreover, these cases suggest that the concomitant diagnosis of MM and PHTP may not be so rare and should be considered for the clinical management of MM patients with hypercalcemia.


Asunto(s)
Hiperparatiroidismo Primario/diagnóstico , Mieloma Múltiple/diagnóstico , Anciano , Antineoplásicos/uso terapéutico , Femenino , Humanos , Hiperparatiroidismo Primario/complicaciones , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/tratamiento farmacológico , Hormona Paratiroidea/sangre , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Receptor de Hormona Paratiroídea Tipo 1/metabolismo , Sindecano-1/metabolismo
7.
Nutr Metab Cardiovasc Dis ; 31(5): 1375-1390, 2021 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-33812734

RESUMEN

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects. Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Osteoporosis/etiología , Densidad Ósea , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea , Consenso , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diagnóstico Precoz , Control Glucémico/efectos adversos , Humanos , Hipoglucemiantes/efectos adversos , Resistencia a la Insulina , Osteoporosis/diagnóstico , Osteoporosis/prevención & control , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Medición de Riesgo , Factores de Riesgo , Resultado del Tratamiento
8.
J Endocrinol Invest ; 44(12): 2575-2579, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33844165

RESUMEN

OBJECTIVE: Graves' orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. METHODS: Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. RESULTS: The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. CONCLUSIONS: The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.


Asunto(s)
Técnicas de Ablación/métodos , Glucocorticoides/administración & dosificación , Oftalmopatía de Graves , Radioisótopos de Yodo/uso terapéutico , Tiroidectomía/métodos , Administración Intravenosa , Terapia Combinada , Relación Dosis-Respuesta en la Radiación , Femenino , Oftalmopatía de Graves/sangre , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/terapia , Humanos , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Masculino , Persona de Mediana Edad , Dosis de Radiación , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
9.
Aging Clin Exp Res ; 33(12): 3223-3235, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33909280

RESUMEN

BACKGROUND: A low calcium intake is a well-known factor that influences the bone mineral density (BMD) maintenance. In the presence of inadequate calcium intake, secondary hyperparathyroidism develops, leading to an increased bone turnover and fracture risk. AIMS: To assess the dietary calcium intake in relation with osteoporosis and fragility fracture in a cohort of Italian individuals evaluated for low BMD. METHODS: A 7-day food-frequency questionnaire was administered to 1793 individuals, who were consecutively referred at the Centers of the Italian Society for Osteoporosis, Mineral Metabolism and Skeletal Diseases (SIOMMMS) for low BMD. RESULTS: In 30.3% and 20.9% of subjects, the calcium intake was inadequate (< 700 mg/day) and adequate (> 1200 mg/day), respectively. As compared with patients with adequate calcium intake, those with inadequate calcium intake were younger (65.5 ± 10.8 vs 63.9 ± 11.5 years, p = 0.03) and they more frequently reported adverse reactions to food (3.2% vs 7.2% p = 0.01) and previous major fragility fractures (20.8% vs 27.0%, p = 0.03). Patients with calcium intake < 700 mg/day showed a higher prevalence of diabetes mellitus, idiopathic hypercalciuria and food allergy/intolerance (8.1%, 5.1%, 7.2%, respectively) than patients with calcium intake > 700 mg/day (5.3%, 3.0%, 4.1%, respectively, p < 0.04 for all comparisons), also after adjusting for age, gender and body mass index. In 30.3% of fractured subjects, the calcium intake was < 700 mg/day. DISCUSSION: In Italy, a low calcium intake is highly prevalent in individuals at risk for low BMD. Importantly, an inadequate calcium intake is highly prevalent even in patients with history of fragility fractures. CONCLUSIONS: Only about a fifth of patients being assessed for low BMD in an Italian SIOMMMS referral Centre have an adequate calcium intake.


Asunto(s)
Enfermedades Óseas Metabólicas , Calcio de la Dieta/administración & dosificación , Fracturas Óseas , Osteoporosis , Densidad Ósea , Fracturas Óseas/epidemiología , Humanos , Italia , Osteoporosis/epidemiología
10.
Int J Mol Sci ; 21(18)2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32967315

RESUMEN

Osteoporosis (OP) is a multifactorial disorder in which environmental factors along with genetic variants and epigenetic mechanisms have been implicated. Long non-coding RNAs (lncRNAs) have recently emerged as important regulators of bone metabolism and OP aetiology. In this study, we analyzed the expression level and the genetic association of lncRNA GAS5 in OP patients compared to controls. Quantitative RT-PCR analysis of GAS5 was performed on the serum of 56 OP patients and 28 healthy individuals. OP subjects were divided into three groups of analysis: 29 with fragility fractures of lumbar spine (OP_VF), 14 with fragility fractures of femoral neck (OP_FF) and 13 without fractures (OP_WF). Genotyping of the rs145204276 insertion/deletion polymorphism has also been performed by Restriction fragment length polymorphism (RFLP) and direct sequencing analyses. Expression of circulating GAS5 is significantly increased in OP patients compared to controls (p < 0.01), with a statistically higher significance in fractured OP individuals vs. healthy subjects (p < 0.001). No statistically significant change was found in female OP patients; conversely, GAS5 is upregulated in the subgroup of fractured OP women sera (p < 0.01) and in all OP males (p < 0.05). Furthermore, a direct correlation between GAS5 expression level and parathyroid hormone (PTH) concentration was found in OP patients (r = 0.2930; p = 0.0389). Genetic analysis of rs145204276 revealed that the deletion allele was correlated with a higher expression of GAS5 in OP patients (0.22 ± 0.02 vs. 0.15 ± 0.01, ** p < 0.01). Our results suggest circulating GAS5 as a putative biomarker for the diagnosis and prognosis of OP and OP-related fractures.


Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , Regulación de la Expresión Génica , Osteoporosis/sangre , Fracturas Osteoporóticas/sangre , ARN Largo no Codificante/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
12.
Calcif Tissue Int ; 103(2): 151-163, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29511787

RESUMEN

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.


Asunto(s)
Bases de Datos Factuales , Hipoparatiroidismo/diagnóstico , Hipoparatiroidismo/epidemiología , Adolescente , Adulto , Anciano , Calcio/sangre , Niño , Enfermedad Crónica , Recolección de Datos/métodos , Endocrinología/métodos , Endocrinología/organización & administración , Femenino , Humanos , Hipocalcemia/sangre , Italia/epidemiología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Fosfatos/sangre , Prevalencia , Estudios Retrospectivos , Adulto Joven
13.
Horm Metab Res ; 50(12): 887-893, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30096720

RESUMEN

Based on the role of oxidative stress in the pathogenesis of Graves' hyperthyroidism and Graves' orbitopathy, the use of the antioxidant agent selenium has been proposed and several studies on the subject have been conducted, both in vitro and in vivo. Whereas a true benefit related to the use of selenium in patients with Graves' hyperthyroidism has been questioned, its use in patients with mild Graves' orbitopathy is generally believed to be beneficial because of which selenium has entered in the clinical practice for this eye condition.


Asunto(s)
Oftalmopatía de Graves/tratamiento farmacológico , Selenio/uso terapéutico , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Humanos , Estrés Oxidativo , Calidad de Vida , Selenio/farmacología , Encuestas y Cuestionarios
14.
Ophthalmic Plast Reconstr Surg ; 34(4S Suppl 1): S105-S110, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29933354

RESUMEN

PURPOSE: To review the in vitro and in vivo studies supporting a role of selenium for the treatment of mild Graves orbitopathy. METHODS: Review of the current literature on the role of selenium in the management of Graves orbitopathy. RESULTS: Graves orbitopathy (GO) is a disfiguring and disabling disorder usually observed in patients with Graves hyperthyroidism, and more rarely in patients with hypothyroid autoimmune thyroiditis or in the absence of overt thyroid dysfunction. Noninvasive treatments include intravenous glucocorticoids and orbital radiotherapy and are generally offered to patients with moderately severe GO. In contrast, patients with mild GO are generally treated only with local measures. Thus, the benefits of intravenous glucocorticoids in mild GO are limited and do not justify the risks that the treatment carries. However, a medical treatment for mild GO is heavily wanted, as a relevant proportion of patients have a significant decrease in their quality of life, and GO can progress into more severe forms. Because of the role of oxidative stress in the pathogenesis of GO, an antioxidant approach has been proposed and the antioxidant agent selenium has been shown to be effective for GO. CONCLUSION: Studies have shown that a 6-month course of sodium selenite can improve the course of mild GO and prevent deterioration when compared with placebo.


Asunto(s)
Manejo de la Enfermedad , Oftalmopatía de Graves/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Ácido Selenioso/uso terapéutico , Oftalmopatía de Graves/metabolismo , Humanos , Oligoelementos/uso terapéutico , Resultado del Tratamiento
15.
Endocr Pract ; 22(10): 1177-1186, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27732097

RESUMEN

OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. METHODS: We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. RESULTS: GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. CONCLUSION: Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ABBREVIATIONS: ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.


Asunto(s)
Glucocorticoides/administración & dosificación , Oftalmopatía de Graves/tratamiento farmacológico , Metimazol/administración & dosificación , Administración Intravenosa , Adulto , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/efectos adversos , Oftalmopatía de Graves/diagnóstico , Oftalmopatía de Graves/radioterapia , Humanos , Masculino , Metimazol/efectos adversos , Persona de Mediana Edad , Pronóstico , Quimioterapia por Pulso , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
16.
Qual Life Res ; 24(3): 769-80, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25194574

RESUMEN

BACKGROUND AND PURPOSE: Thyroid diseases are common and often affect quality of life (QoL). No cross-culturally validated patient-reported outcome measuring thyroid-related QoL is available. The purpose of the present study was to test the cross-cultural validity of the newly developed thyroid-related patient-reported outcome ThyPRO, using tests for differential item functioning (DIF) according to language version. METHODS: The ThyPRO consists of 85 items summarized in 13 multi-item scales and one single item. Scales cover physical and mental symptoms, well-being and function as well as social and daily function and cosmetic concerns. Translation applied standard forward-backward methodology with subsequent cognitive interviews and reviews. Responses (N = 1,810) to the ThyPRO were collected in seven countries: UK (n = 166), The Netherlands (n = 147), Serbia (n = 150), Italy (n = 110), India (n = 148), Denmark (n = 902) and Sweden (n = 187). Translated versions were compared pairwise to the English version by examining uniform and nonuniform DIF, i.e., whether patients from different countries respond differently to a particular item, although they have identical level of the concept measured by the item. Analyses were controlled for thyroid diagnosis. DIF was investigated by ordinal logistic regression, testing for both statistical significance and magnitude (ΔR (2) > 0.02). Scale level was estimated by the sum score, after purification. RESULTS: For twelve of the 84 tested items, DIF was identified in more than one language. Eight of these were small, but four were indicative of possible low translatability. Twenty-one instances of DIF in single languages were identified, indicating potential problems with the particular translation. However, only seven were of a magnitude which could affect scale scores, most of which could be explained by sample differences not controlled for. CONCLUSION: The ThyPRO has good cross-cultural validity with only minor cross-cultural invariance and is recommended for use in international multicenter studies.


Asunto(s)
Comparación Transcultural , Evaluación del Resultado de la Atención al Paciente , Calidad de Vida/psicología , Autoinforme , Enfermedades de la Tiroides/terapia , Adulto , Cultura , Dinamarca , Femenino , Humanos , India , Italia , Lenguaje , Modelos Logísticos , Masculino , Persona de Mediana Edad , Países Bajos , Satisfacción Personal , Serbia , Encuestas y Cuestionarios , Suecia , Enfermedades de la Tiroides/diagnóstico , Traducciones
17.
World J Surg Oncol ; 13: 270, 2015 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-26350418

RESUMEN

Parathyroid carcinoma (PC) is a rare endocrine malignancy. The tumor is mostly functioning, causing severe primary hyperparathyroidism, with high serum calcium and parathyroid hormone (PTH) levels. Nonfunctioning PC is extremely rare. We report a 50-year-old male patient who was referred to our Department for a right thyroid nodule, incidentally detected on carotid Doppler ultrasound scan, with a fine-needle aspiration cytology showing a follicular lesion. At the time of our evaluation, neck ultrasound showed a 1.3 cm right hypoechoic thyroid nodule with irregular margins and the absence of enlarged bilateral cervical lymph nodes. Thyroid function tests were normal. Serum calcium was normal and plasma PTH slightly above the upper limit of the normal range. The patients underwent right lobectomy. The intraoperative frozen-section pathological examination raised the suspicion of a PC. Definitive histology showed a markedly irregular infiltrative growth of the tumor with invasion of the thyroid tissue and cervical soft tissues. Immunostaining for thyroglobulin was negative, whereas staining for chromogranin A and PTH showed a strong reactivity. Based on the microscopic findings and the immunohistochemical profile, the tumor was diagnosed as a PC. Postoperative serum calcium and phosphate levels were in the normal range. One month after surgery, serum calcium and PTH were normal. Neck ultrasound and total body computed tomography scan were negative for local and metastatic disease. Eight months later, serum calcium was normal and plasma PTH level remained around the upper limit of normal range. Neck ultrasound did not show any pathological lesions. This is the first case of a nonfunctioning sporadic PC misdiagnosed prior of surgery as a follicular thyroid nodule. The parathyroid nature of the neck lesion could not be suspected before surgery. Fine-needle aspiration cytology (FNAC) may fail to distinguish a parathyroid tumor from a benign thyroid nodule because at FNAC, parathyroid and thyroid lesions have some morphological similarities. Histological criteria are not always sufficient for the differential diagnosis, which can definitely be established using immunohistochemistry.


Asunto(s)
Adenocarcinoma Folicular/diagnóstico , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de la Tiroides/diagnóstico , Nódulo Tiroideo/diagnóstico , Diagnóstico Diferencial , Errores Diagnósticos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico
18.
J Cell Mol Med ; 18(10): 1944-52, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25164318

RESUMEN

The parathyroid glands play an overall regulatory role in the systemic calcium (Ca(2+)) homeostasis. The purpose of the present study was to demonstrate the presence of the Ca(2+) channels transient receptor potential vanilloid (TRPV) 5 and TRPV6 in human parathyroid glands. Semi-quantitative and quantitative PCR was carried out to evaluate the presence of TRPV5 and TRPV6 mRNAs in sporadic parathyroid adenomas and normal parathyroid glands. Western blot and immunocytochemical assays were used to assess protein expression, cellular localization and time expression in primary cultures from human parathyroid adenoma. TRPV5 and TRPV6 transcripts were then identified both in normal and pathological tissues. Predominant immunoreactive bands were detected at 75-80 kD for both vanilloid channels. These channels co-localized with the calcium-sensing receptor (CASR) on the membrane surface, but immunoreactivity was also detected in the cytosol and around the nuclei. Our data showed that western blotting recorded an increase of protein expression of both channels in adenoma samples compared with normal glands suggesting a potential relation with the cell calcium signalling pathway and the pathological processes of these glands.


Asunto(s)
Adenoma/patología , Canales de Calcio/metabolismo , Transformación Celular Neoplásica/patología , Hiperparatiroidismo Primario/patología , Glándulas Paratiroides/metabolismo , Canales Catiónicos TRPV/metabolismo , Adenoma/genética , Adenoma/metabolismo , Western Blotting , Calcio/metabolismo , Canales de Calcio/genética , Membrana Celular/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Células Cultivadas , Humanos , Hiperparatiroidismo Primario/genética , Hiperparatiroidismo Primario/metabolismo , Técnicas para Inmunoenzimas , Glándulas Paratiroides/citología , Técnicas de Placa-Clamp , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Sensibles al Calcio/genética , Receptores Sensibles al Calcio/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Canales Catiónicos TRPV/genética
19.
N Engl J Med ; 364(20): 1920-31, 2011 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-21591944

RESUMEN

BACKGROUND: Oxygen free radicals and cytokines play a pathogenic role in Graves' orbitopathy. METHODS: We carried out a randomized, double-blind, placebo-controlled trial to determine the effect of selenium (an antioxidant agent) or pentoxifylline (an antiinflammatory agent) in 159 patients with mild Graves' orbitopathy. The patients were given selenium (100 µg twice daily), pentoxifylline (600 mg twice daily), or placebo (twice daily) orally for 6 months and were then followed for 6 months after treatment was withdrawn. Primary outcomes at 6 months were evaluated by means of an overall ophthalmic assessment, conducted by an ophthalmologist who was unaware of the treatment assignments, and a Graves' orbitopathy-specific quality-of-life questionnaire, completed by the patient. Secondary outcomes were evaluated with the use of a Clinical Activity Score and a diplopia score. RESULTS: At the 6-month evaluation, treatment with selenium, but not with pentoxifylline, was associated with an improved quality of life (P<0.001) and less eye involvement (P=0.01) and slowed the progression of Graves' orbitopathy (P=0.01), as compared with placebo. The Clinical Activity Score decreased in all groups, but the change was significantly greater in the selenium-treated patients. Exploratory evaluations at 12 months confirmed the results seen at 6 months. Two patients assigned to placebo and one assigned to pentoxifylline required immunosuppressive therapy for deterioration in their condition. No adverse events were evident with selenium, whereas pentoxifylline was associated with frequent gastrointestinal problems. CONCLUSIONS: Selenium administration significantly improved quality of life, reduced ocular involvement, and slowed progression of the disease in patients with mild Graves' orbitopathy. (Funded by the University of Pisa and the Italian Ministry for Education, University and Research; EUGOGO Netherlands Trial Register number, NTR524.).


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Oftalmopatía de Graves/tratamiento farmacológico , Pentoxifilina/uso terapéutico , Calidad de Vida , Selenio/uso terapéutico , Adulto , Antiinflamatorios/efectos adversos , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Masculino , Pentoxifilina/efectos adversos
20.
Artículo en Inglés | MEDLINE | ID: mdl-38940486

RESUMEN

CONTEXT: Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or distant metastasis, leading to uncertainty regarding its malignant potential. OBJECTIVE: To characterize the molecular landscape and deregulated pathways in APT. METHODS: Whole exome sequencing (WES) was conducted on 16 APTs. DNA from tumors and matched peripheral blood underwent WES using Illumina HiSeq3000. RESULTS: A total of 192 nonsynonymous variants were identified. The median number of protein-altering mutations was 9. The most frequently mutated genes included BCOR, CLMN, EZH1, JAM2, KRTAP13-3, MUC16, MUC19, and OR1S1. Seventeen mutated genes belong to the Cancer Gene Census list. The most consistent hub genes identified through STRING network analysis were ATM, COL4A5, EZH2, MED12, MEN1, MTOR, PI3, PIK3CA, PIK3CB, and UBR5. Deregulated pathways included the PI3 K/AKT/mTOR pathway, Wnt signaling, and extracellular matrix organization. Variants in genes such as MEN1, CDC73, EZH2, PIK3CA, and MTOR, previously reported as established or putative/candidate driver genes in benign adenoma (PA) and/or PC, were also identified in APT. CONCLUSIONS: APT does not appear to have a specific molecular signature but shares genomic alterations with both PA and PC. The incidence of CDC73 mutations is low, and it remains unclear whether these mutations are associated with a higher risk of recurrence. Our study confirms that PI3 K/AKT/mTOR and Wnt signaling represents the pivotal pathways in parathyroid tumorigenesis and also revealed mutations in key epigenetic modifier genes (BCOR, KDM2A, MBD4, and EZH2) involved in chromatin remodeling, DNA, and histone methylation.

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