Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease / El test de la desmopresina en el diagnóstico y seguimiento de la enfermedad de Cushing cíclica

OBJECTIVE: To assess the utility of the desmopressin (DDAVP) test in the diagnosis and follow-up of a cyclical Cushing's disease (CCS) case. MATERIAL AND METHODS: Laboratory tests included morning and midnight serum cortisol levels, 24 h urine free cortisol excretion, midnight salivary cortisol levels, serum cortisol levels after low (1 mg) and high (8 mg) dexamethasone, plasma ACTH and serum cortisol levels after DDAVP. Magnetic resonance imaging (MRI) was used to assess the presence of a pituitary adenoma. The resected tumor specimen was studied by histological, immunohistochemical and cell biology techniques. RESULTS: A patient was referred to our unit with a diagnosis of Cushing's syndrome (CS) for further evaluation and treatment. However, no biochemical evidence of hypercortisolism was observed in the follow-up evaluations. Furthermore, the typical features of CS fluctuated throughout this period. A consistent positive response to the DDAVP stimulation test was observed during the diagnostic work-up, even when overt clinical features of CS were not apparent, raising suspicion for CCS. After two years of follow-up a definitive diagnosis of hypercortisolism was established. An MRI scan revealed a pituitary adenoma, as the source of ACTH production. After transphenoidal surgery, clinical signs of CS resolved and the response to DDAVP became negative. DDAVP induced a significant increase in ACTH levels in cultured pituitary adenoma cells, consistent with the in vivo DDAVP test results. CONCLUSIONS: Our case illustrates the utility of the DDAVP test in the evaluation of patients with suspected CCS. The DDAVP test could facilitate the management of CCS by shortening the time of diagnosis

OBJETIVO: Evaluar la utilidad de la prueba de la desmopresina (DDAVP) en el diagnóstico y seguimiento de un caso de enfermedad de Cushing cíclica (ECC). MATERIAL Y MÉTODO: Se realizaron mediciones de cortisol sérico diurno y nocturno, cortisol libre en orina de 24 h, cortisol en saliva nocturno, cortisol sérico tras dosis elevadas y bajas de dexametasona, ACTH plasmática y cortisol tras la DDAVP, y resonancia magnética (RM) para valorar la presencia de un adenoma hipofisario. El tumor extirpado fue analizado mediante técnicas histológicas, inmunohistoquímicas y de biología celular. RESULTADOS: Se presenta una paciente enviada a nuestra unidad con el diagnóstico de síndrome de Cushing (SC) para evaluación más completa y tratamiento. No obstante durante un periodo de seguimiento de 2 años no se encontró evidencia alguna de hipercortisolismo en los análisis realizados en nuestro laboratorio. Durante este tiempo, la paciente mostró fluctuaciones de los síntomas y signos típicos del SC. De manera interesante, la prueba de DDAVP mostró hiperrespuesta de cortisol y ACTH en todas las evaluaciones. La exploración por RM mostró un adenoma hipofisario que tras extirpación resultó ser positivo para ACTH. El SC se resolvió tras la cirugía y la respuesta a la prueba de DDAVP desapareció en las evaluaciones de seguimiento posquirúrgico. Se incubaron muestras del tumor mostrando este un aumento en la secreción in vitro de ACTH. CONCLUSIONES: Este caso ilustra la utilidad de la prueba de DDAVP en la evaluación de pacientes con sospecha de SCC. Esta prueba podría facilitar el manejo del SCC acortando el tiempo de diagnóstico

Desmopressin test in the diagnosis and follow-up of cyclical Cushing's disease.

OBJECTIVE: To assess the utility of the desmopressin (DDAVP) test in the diagnosis and follow-up of a cyclical Cushing's disease (CCS) case. MATERIAL AND METHODS: Laboratory tests included morning and midnight serum cortisol levels, 24h urine free cortisol excretion, midnight salivary cortisol levels, serum cortisol levels after low (1 mg) and high (8 mg) dexamethasone, plasma ACTH and serum cortisol levels after DDAVP. Magnetic resonance imaging (MRI) was used to assess the presence of a pituitary adenoma. The resected tumor specimen was studied by histological, immunohistochemical and cell biology techniques. RESULTS: A patient was referred to our unit with a diagnosis of Cushing's syndrome (CS) for further evaluation and treatment. However, no biochemical evidence of hypercortisolism was observed in the follow-up evaluations. Furthermore, the typical features of CS fluctuated throughout this period. A consistent positive response to the DDAVP stimulation test was observed during the diagnostic work-up, even when overt clinical features of CS were not apparent, raising suspicion for CCS. After two years of follow-up a definitive diagnosis of hypercortisolism was established. An MRI scan revealed a pituitary adenoma, as the source of ACTH production. After transphenoidal surgery, clinical signs of CS resolved and the response to DDAVP became negative. DDAVP induced a significant increase in ACTH levels in cultured pituitary adenoma cells, consistent with the in vivo DDAVP test results. CONCLUSIONS: Our case illustrates the utility of the DDAVP test in the evaluation of patients with suspected CCS. The DDAVP test could facilitate the management of CCS by shortening the time of diagnosis.

Mantenimiento a largo plazo con dosis bajas de fármacos antitiroideos de síntesis frente a retirada, en pacientes con hipertiroidismo de la enfermedad de Graves / Long-term maintenance of low-dose antithyroid drugs versus drug withdrawal in patients with Graves’ hyperthyroidism

Objetivo: La recurrencia del hipertiroidismo de la enfermedad de Graves tras dar por finalizado un ciclo de antitiroideos, es frecuente. El objetivo de este trabajo es investigar de forma prospectiva la recaída del hipertiroidismo durante el mantenimiento de 5 años con dosis bajas de fármacos antitiroideos de síntesis. Material y método: Desde marzo de 1997 se reclutó para la intervención a todos los pacientes con hipertiroidismo de la enfermedad de Graves que acudían consecutivamente a una misma consulta, y habían alcanzado el eutiroidismo con dosis bajas de antitiroideos (2,5-5 mg/día de carbimazol o metimazol) en 2 revisiones sucesivas (10-12 meses). Se intentó mantener desde entonces, en lugar de suspenderlo, un tratamiento con estas dosis durante 5 años, y se estudió en ese intervalo la tasa de recaída del hipertiroidismo (grupo M, 53 pacientes). Desde la misma fecha (marzo de 1997), se recogieron también datos de los pacientes con hipertirodismo de la enfermedad de Graves que se revisaban consecutivamente en dicha consulta, pero a los que, con anterioridad a esa fecha, se les había suspendido la medicación antitiroidea al conseguir las mismas condiciones señaladas anteriormente; de igual modo se estudió la tasa de recurrencia del hipertiroidismo durante los 5 años que seguían a la suspensión (grupo R, histórico, control, 31 pacientes). Resultado principal: El hipertiroidismo recayó en 12/53 (22,64%) pacientes del grupo M, por 24/31 (77,42%) pacientes del grupo R (p < 0,000). Conclusiones: La tasa de recaída del hipertiroidismo de la enfermedad de Graves mientras se mantenían dosis bajas de fármacos antitiroideos de síntesis fue menor, de forma significativa, que la recogida tras suspenderlos (AU)

Objective: The relapse rate of Graves' hyperthyroidism after finishing an antithyroid cicle is high. The objective of this work was to prospectively investigate the relapse rate of Graves' hyperthyroidism (GH) in patients with maintenance of a low dose of antithyroid drug (ATD) therapy. Patients and method: From March 1997, all patients with GH consecutively attending the same center who remained euthyroid with low doses of synthetic ATD (carbimazole or methimazole: 2.5-5 mg/day) on 2 consecutive follow-up visits (at 10-12 months) were included in this study. Instead of withdrawing ATD, the aim was to continue with this low dose for a 5-year period (group M: 53 patients). From March 1997, data were also collected from patients with GH who were consecutively followed-up and who, meeting the criteria for inclusion in group M, had stopped receiving ATD before the start of the study (March 1997) (group R: 31 patients). Main outcome: GH relapse was observed in 12/53 patients in group M (22.64%) and in 24/31 patients in group R (77.42%) (p < 0.000). Conclusions: The GH relapse rate was significantly lower with long-term maintenance of a low dose of ATD than with therapy withdrawal (AU)

Long-term maintenance of low-dose antithyroid drugs versus drug withdrawal in patients with Graves' hyperthyroidism.

OBJECTIVE: The relapse rate of Graves' hyperthyroidism after finishing an antithyroid cicle is high. The objective of this work was to prospectively investigate the relapse rate of Graves' hyperthyroidism (GH) in patients with maintenance of a low dose of antithyroid drug (ATD) therapy. PATIENTS AND METHOD: From March 1997, all patients with GH consecutively attending the same center who remained euthyroid with low doses of synthetic ATD (carbimazole or methimazole: 2.5-5mg/day) on 2 consecutive follow-up visits (at 10-12 months) were included in this study. Instead of withdrawing ATD, the aim was to continue with this low dose for a 5-year period (group M: 53 patients). From March 1997, data were also collected from patients with GH who were consecutively followed-up and who, meeting the criteria for inclusion in group M, had stopped receiving ATD before the start of the study (March 1997) (group R: 31 patients). MAIN OUTCOME: GH relapse was observed in 12/53 patients in group M (22.64%) and in 24/31 patients in group R (77.42%) (p<0.000). CONCLUSIONS: The GH relapse rate was significantly lower with long-term maintenance of a low dose of ATD than with therapy withdrawal.