RESUMEN
BACKGROUND: Dopamine agonists (DA) are the first-line therapy in prolactinomas, but they fail to decrease prolactin (PRL) levels and/or tumor size in some of these tumors, which are labeled as resistant prolactinomas (RP). To date, risk factors for DA resistance are not fully understood and management of DA-RP is not well established. METHODS: We retrospectively recorded clinical, biochemical and radiological features, as well as management and outcome, of all cabergoline (CAB)-RP attended at the Endocrinology department of a tertiary hospital between 1995 and 2016. CAB resistance was defined as the failure to normalize PRL (biochemical resistance, BR) or reduce tumor size by at least 50% (morphological resistance, MR) with a CAB dose up to 2mg/week (or 3mg/week in cases where lower doses were not tested) for at least 3 months. RESULTS: Ten CAB-RP were found. The mean age of the cohort was 30.6 years and 50% of subjects were male. The average tumor size was 1.78cm (80% macroadenomas). The mean maximal dose of CAB was 3.8mg/week. Five patients showed isolated MR, four combined MR+BR and only one isolated BR. MR patients were more often males and older than MR+BR patients. Transsphenoidal surgery achieved normalization of PRL and/or disappearance of tumor in three of seven patients. At the end of follow up all patients had controlled PRL levels (with or without CAB) and most of them bore a visible although stable tumor. CONCLUSIONS: Isolated MR and combined MR+BR are the most frequent patterns of DA resistance whereas isolated BR seems to be uncommon. Our data support a high tumor size but not male gender as a risk factor for DA resistance.
Asunto(s)
Cabergolina/uso terapéutico , Agonistas de Dopamina/uso terapéutico , Resistencia a Antineoplásicos , Neoplasias Hipofisarias/tratamiento farmacológico , Prolactinoma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Neoplasias Hipofisarias/genética , Prolactinoma/genética , Estudios RetrospectivosRESUMEN
OBJECTIVES: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline® Autogel®). METHODS: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. RESULTS: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. CONCLUSIONS: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals.
Asunto(s)
Acromegalia/sangre , Acromegalia/tratamiento farmacológico , Hormona de Crecimiento Humana/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Péptidos Cíclicos/administración & dosificación , Somatostatina/análogos & derivados , Adulto , Anciano , Anciano de 80 o más Años , Esquema de Medicación , Femenino , Geles , Humanos , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Valores de Referencia , Estudios Retrospectivos , Somatostatina/administración & dosificación , Factores de Tiempo , Adulto JovenRESUMEN
INTRODUCTION: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. METHODS: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. RESULTS: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840µg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. CONCLUSIONS: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended.
Asunto(s)
Síndrome de ACTH Ectópico/complicaciones , Síndrome de Cushing/etiología , Neoplasias Pancreáticas/complicaciones , Síndrome de ACTH Ectópico/tratamiento farmacológico , Síndrome de ACTH Ectópico/cirugía , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tumor Carcinoide/complicaciones , Tumor Carcinoide/tratamiento farmacológico , Tumor Carcinoide/secundario , Tumor Carcinoide/cirugía , Carcinoma de Células Pequeñas/complicaciones , Carcinoma de Células Pequeñas/secundario , Carcinoma de Células Pequeñas/cirugía , Terapia Combinada , Femenino , Gastrinoma/complicaciones , Gastrinoma/diagnóstico , Gastrinoma/tratamiento farmacológico , Gastrinoma/secundario , Humanos , Hidrocortisona/orina , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirugía , Feocromocitoma/complicaciones , Feocromocitoma/cirugía , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias del Timo/complicaciones , Neoplasias del Timo/tratamiento farmacológico , Neoplasias del Timo/cirugía , Adulto JovenRESUMEN
Introducción: El síndrome de Cushing ectópico (SCE) es una entidad rara debida a la secreción de ACTH por tumores extrahipofisarios. Su baja frecuencia dificulta la adquisición de experiencia en su manejo. El objetivo de este trabajo es describir a los pacientes con SCE atendidos en el servicio de Endocrinología en un hospital de tercer nivel en un periodo de 15 años. Métodos: Se trata de un estudio retrospectivo de los datos clínicos, bioquímicos y radiológicos, tratamiento recibido, y evolución de los pacientes con SCE atendidos entre los años 2000 y 2015. Resultados: Se incluyeron 9 pacientes (6 mujeres) con una edad media de 47 años. El síndrome clínico se desarrolló en un tiempo inferior a 3 meses en todos los casos excepto en uno, y la mayoría presentaba edemas, hiperpigmentación y/o hipopotasemia. La media del cortisol libre urinario y de la ACTH fue de 2.840μg/24h y 204pg/ml, respectivamente. El origen ectópico se confirmó por la combinación de pruebas dinámicas no invasivas y estudios radiológicos en la mayoría de los casos. El tumor responsable pudo identificarse en 8 casos y 7 presentaban diseminación metastásica. El tratamiento primario consistió en cirugía en un caso, cirugía más terapia sistémica en 3 y quimioterapia en otros 3. En 4 pacientes fue necesaria la suprarrenalectomía bilateral para controlar el hipercortisolismo. Tras un seguimiento medio de 40 meses, 3 habían fallecido, 5 permanecían vivos y en uno se había perdido el seguimiento. Conclusiones: Se confirma que el SCE abarca un amplio espectro de tumores de diferente agresividad y naturaleza. Habitualmente el origen ectópico del síndrome de Cushing puede sospecharse y confirmarse en la mayoría de los casos sin necesidad de pruebas invasivas. Tanto el control del hipercortisolismo como del tumor requieren múltiples modalidades terapéuticas, siendo recomendable el manejo multidisciplinar
Introduction: Ectopic Cushing's syndrome (ECS) is a rare condition caused by ACTH secretion by extrapituitary tumors. Its low frequency makes it difficult to acquire experience in its management. The aim of this study was to describe patients with ECS seen at the endocrinology department of a tertiary hospital over 15 years. Methods: This was a retrospective study of the clinical, biochemical and radiographic data, treatment, and course of patients with ECS seen from 2000 to 2015. Results: Nine patients (6 of them female) with a mean age of 47 years were included in the study. The clinical syndrome developed in less than 3 months in all cases but one, and most patients also had edema, hyperpigmentation and/or hypokalemia. Mean urinary free cortisol and ACTH levels were 2,840μg/24h and 204pg/mL respectively. The ectopic origin was confirmed by a combination of dynamic non-invasive tests and radiographic studies in most cases. The tumor responsible could be identified in 8 cases, and 7 patients had metastatic dissemination. Primary treatment was surgery in one patient, surgery combined with systemic therapy in 3, and chemotherapy in the other 3 patients. Bilateral adrenalectomy was required in 4 patients to control hypercortisolism. After a mean follow-up of 40 months, 3 patients died, 5 were still alive, and one had been lost to follow-up. Conclusions: Our study confirms that ECS covers a wide spectrum of tumors of different aggressiveness and nature. The ectopic origin of Cushing's syndrome can usually, be suspected and confirmed in most cases without the need for invasive tests. Control of both hypercortisolism and the tumor requires multiple treatment modalities, and multidisciplinary management is recommended
Asunto(s)
Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Síndrome de Cushing/diagnóstico , Hiperfunción de las Glándulas Suprarrenales/fisiopatología , Síndrome de ACTH Ectópico , Síndrome de Cushing/tratamiento farmacológico , Síndrome de Cushing/cirugía , Tumores Neuroendocrinos , Diagnóstico por Imagen/métodos , Hiperfunción de las Glándulas Suprarrenales/tratamiento farmacológicoRESUMEN
Background: Dopamine agonists (DA) are the first-line therapy in prolactinomas, but they fail to decrease prolactin (PRL) levels and/or tumor size in some of these tumors, which are labeled as resistant prolactinomas (RP). To date, risk factors for DA resistance are not fully understood and management of DA-RP is not well established. Methods: We retrospectively recorded clinical, biochemical and radiological features, as well as management and outcome, of all cabergoline (CAB)-RP attended at the Endocrinology department of a tertiary hospital between 1995 and 2016. CAB resistance was defined as the failure to normalize PRL (biochemical resistance, BR) or reduce tumor size by at least 50% (morphological resistance, MR) with a CAB dose up to 2 mg/week (or 3 mg/week in cases where lower doses were not tested) for at least 3 months. Results: Ten CAB-RP were found. The mean age of the cohort was 30.6 years and 50% of subjects were male. The average tumor size was 1.78 cm (80% macroadenomas). The mean maximal dose of CAB was 3.8 mg/week. Five patients showed isolated MR, four combined MR + BR and only one isolated BR. MR patients were more often males and older than MR + BR patients. Transsphenoidal surgery achieved normalization of PRL and/or disappearance of tumor in three of seven patients. At the end of follow up all patients had controlled PRL levels (with or without CAB) and most of them bore a visible although stable tumor. Conclusions: Isolated MR and combined MR + BR are the most frequent patterns of DA resistance whereas isolated BR seems to be uncommon. Our data support a high tumor size but not male gender as a risk factor for DA resistance
Contexto: Los agonistas dopaminérgicos (AD) son el tratamiento de elección de los prolactinomas, pero en algunos casos no logran normalizar los niveles de prolactina (PRL) o disminuir el tamaño del tumor, y estos casos se etiquetan como prolactinomas resistentes (PR). Los factores de riesgo de resistencia a los AD y el manejo de los PR no están bien establecidos. Métodos: Analizamos retrospectivamente las características clínicas, bioquímicas y radiológicas, así como el manejo y evolución de los PR a cabergolina (CAB) atendidos en el departamento de Endocrinología de un hospital terciario entre 1995 y 2016. La resistencia a CAB se definió como persistencia de PRL elevada (resistencia bioquímica, RB) o reducción tumoral inferior al 50% (resistencia morfológica, RM) tras al menos 3 meses de tratamiento con una dosis de CAB de hasta 2 mg/semana (o 3 mg/semana en los casos que no recibieron dosis inferiores) Resultados: Se incluyeron 10 pacientes, edad media 30.6 años, 50% varones. El tamaño medio del tumor fue 1.78 cm (80% macroadenomas) y la dosis máxima media de CAB 3.8 mg/semana. Cinco pacientes presentaron RM aislada, cuatro RM + RB y uno RB aislada. La prevalencia de sexo masculino y la edad fueron superiores en el grupo RM comparado con el grupo RM + RB. La cirugía transesfenoidal logró normalización de PRL y/o desaparición del tumor en tres de siete pacientes. Al final del seguimiento la PRL era normal (con o sin CAB) en todos los casos y la mayoría presentaba un tumor visible de tamaño estable. Conclusiones: la RM aislada y la RM+RB combinadas son los patrones más frecuentes de resistencia a los AD. Nuestros datos apoyan la asociación del tamaño tumoral pero no del sexo masculino con la resistencia a los AD
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Prolactinoma/tratamiento farmacológico , Cabergolina/administración & dosificación , Prolactinoma/diagnóstico , Prolactina/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Factores de Riesgo , Estudios Retrospectivos , Prolactinoma/patología , Prolactinoma/cirugía , Hipófisis/diagnóstico por imagen , Hipófisis/patología , Hipogonadismo/etiologíaRESUMEN
Objectives: The ACROSTART study was intended to determine the time to achieve normalization of GH and IGF-I levels in responding patients with acromegaly administered different dosage regimens of lanreotide Autogel (Somatuline(R) Autogel(R)). Methods: From March 2013 to October 2013, clinical data from 57 patients from 17 Spanish hospitals with active acromegaly treated with lanreotide for ≥4 months who achieved hormonal control (GH levels <2.5ng/ml and/or normalized IGF-I levels in ≥2 measurements) were analyzed. The primary objective was to determine the time from start of lanreotide treatment to hormonal normalization. Results: Median patient age was 64 years, 21 patients were male, 39 patients had undergone surgery, and 14 patients had received radiotherapy. Median hormonal values at start of lanreotide treatment were: GH, 2.6ng/ml; IGF-I, 1.6×ULN. The most common starting dose of lanreotide was 120mg (29 patients). The main initial regimens were 60mg/4 weeks (n=13), 90mg/4 weeks (n=6), 120mg/4 weeks (n=13), 120mg/6 weeks (n=6), and 120mg/8 weeks (n=9). An initial treatment regimen with a long interval (≥6 weeks) was administered in 25 patients. Mean duration of lanreotide treatment was 68 months (7-205). Median time to achieve hormonal control was 4.9 months. Injections were managed without healthcare assistance in 13 patients. Median number of visits to endocrinologists until hormonal control was achieved was 3. Fifty-one patients were "satisfied"/"very satisfied" with treatment and 49 patients did not miss any dose. Conclusions: Real-life treatment with lanreotide Autogel resulted in early hormonal control in responding patients, with high treatment adherence and satisfaction despite disparity in starting doses and dosing intervals
Objetivos: El objetivo del estudio ACROSTART era determinar el período de tiempo para lograr la normalización hormonal (GH e IGF-I) en pacientes con acromegalia respondedores al tratamiento considerando los regímenes de lanreótida Autogel (Somatuline(R) Autogel(R)) utilizados en la práctica clínica. Métodos: Desde marzo de 2013 hasta octubre de 2013, en 17 hospitales españoles se analizaron los datos clínicos de 57 pacientes con acromegalia activa tratados con lanreótida durante ≥4 meses que lograron control hormonal (niveles de GH <2,5ng/ml y/o IGF-I normalizado en ≥2 evaluaciones). El objetivo principal fue determinar el período de tiempo desde el inicio del tratamiento con lanreótida hasta la normalización hormonal. Resultados: La mediana de edad de los pacientes fue 64 años, 21 pacientes eran hombres, 39 pacientes habían recibido cirugía, 14 pacientes habían recibido radioterapia. Los valores hormonales medianos al inicio del tratamiento con lanreótida fueron GH: 2,6ng/ml, IGF-I: 1,6×LSN. La dosis inicial más frecuente de lanreótida fue de 120mg (29 pacientes). Los principales regímenes iniciales fueron 60mg/4 semanas (n=13), 90mg/4 semanas (n=6), 120mg/4 semanas (n=13), 120mg/6 semanas (n=6), 120mg/8 semanas (n=9). Se administró un régimen de intervalo prolongado (≥6 semanas) en 25 pacientes. La duración media del tratamiento con lanreótida fue de 68 meses (7-205). El tiempo medio hasta lograr el control hormonal fue de 4,9 meses. Las inyecciones se manejaron sin asistencia médica en 13 pacientes. La mediana del número de visitas al endocrinólogo hasta el control hormonal fue 3. Cincuenta y un pacientes estaban "satisfechos"/"muy satisfechos" con el tratamiento y 49 pacientes no olvidaron ninguna dosis. Conclusiones: El tratamiento en la vida real con lanreótida Autogel condujo a un control hormonal temprano en pacientes que respondieron, con una alta adherencia al tratamiento y satisfacción con el tratamiento, a pesar de la disparidad de las dosis iniciales y los intervalos de dosificación