The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism.

INTRODUCTION: The Gli family of zinc finger (GLI) transcription factors mediates the sonic hedgehog signalling pathway (HH) essential for CNS, early pituitary and ventral forebrain development in mice. Human mutations in this pathway have been described in patients with holoprosencephaly (HPE), isolated congenital hypopituitarism (CH) and cranial/midline facial abnormalities. Mutations in Sonic hedgehog (SHH) have been associated with HPE but not CH, despite murine studies indicating involvement in pituitary development. OBJECTIVES/METHODS: We aimed to establish the role of the HH pathway in the aetiology of hypothalamo-pituitary disorders by screening our cohort of patients with midline defects and/or CH for mutations in SHH, GLI2, Shh brain enhancer 2 (SBE2) and growth-arrest specific 1 (GAS1). RESULTS: Two variants and a deletion of GLI2 were identified in three patients. A novel variant at a highly conserved residue in the zinc finger DNA-binding domain, c.1552G > A [pE518K], was identified in a patient with growth hormone deficiency and low normal free T4. A nonsynonymous variant, c.2159G > A [p.R720H], was identified in a patient with a short neck, cleft palate and hypogonadotrophic hypogonadism. A 26·6 Mb deletion, 2q12·3-q21·3, encompassing GLI2 and 77 other genes, was identified in a patient with short stature and impaired growth. Human embryonic expression studies and molecular characterisation of the GLI2 mutant p.E518K support the potential pathogenicity of GLI2 mutations. No mutations were identified in GAS1 or SBE2. A novel SHH variant, c.1295T>A [p.I432N], was identified in two siblings with variable midline defects but normal pituitary function. CONCLUSIONS: Our data suggest that mutations in SHH, GAS1 and SBE2 are not associated with hypopituitarism, although GLI2 is an important candidate for CH.

Valoración del estado de ansiedad de los pacientes que reciben un tratamiento con radioyodo o son sometidos a una exploración de ganglio centinela en el servicio de Medicina Nuclear / Evaluation of the anxiety state in patients receiving radioiodine treatment or who undergo a sentinel lymph node examination in the Nuclear Medicine Department

ObjetivoAnalizar la presencia de ansiedad en pacientes derivados a un servicio de Medicina Nuclear (SMN).Material y métodoSe incluyeron 148 pacientes; 67 derivados para tratamiento con radioyodo, 48 con hipertiroidismo (HT), 19 con carcinoma diferenciado de tiroides (CDT) y 81 para detección y biopsia del ganglio centinela (GC) en carcinoma de mama (CM).Material y métodoSe rellenaron los siguientes documentos: datos de filiación, escala de ansiedad estado-rasgo, escala de factores predisponentes ansiógenos y cuestionario de información.Material y métodoSe estudiaron los factores predisponentes ansiógenos y la influencia de la información en el padecimiento de ansiedad.ResultadosUn 47% de los pacientes con HT tenían ansiedad en el momento de la visita, que no se relacionó con el nivel de información recibido. El factor que más les preocupaba era la administración de radioyodo. El hecho de ser la primera visita a un SMN se relacionó estadísticamente (p<0,05) con la aparición de ansiedad.ResultadosEl 42% de los pacientes con CDT tenían ansiedad en el momento de la visita, que no se relacionó con el nivel de información recibido. El factor que más les preocupaba era la propia enfermedad. Ningún factor fue relacionado estadísticamente con la aparición de ansiedad.ResultadosEl 53% de los pacientes con CM tenían ansiedad en el momento de la visita, que no se relacionó con el nivel de información recibido. El factor que más les preocupaba eran los resultados. El antecedente ansioso-depresivo se relacionó estadísticamente (p<0,05) con la aparición de ansiedad.ConclusiónLa cantidad de información proporcionada antes de un procedimiento en un SMN no influye en el padecimiento de ansiedad. No obstante, es nuestro deber dar la mejor información posible(AU)

ObjectiveTo analyze the presence of anxiety in patients referred to a Nuclear Medicine Department (NMD).Material and methodsA total of 148 patients were included: 67 were referred for radioiodine therapy, 48 with hyperthyroidism (HT), 19 with differentiated thyroid carcinoma (DTC), and 81 were referred for detection and biopsy of the sentinel node in breast cancer (BC).Material and methodsThe following documents were filled out: personal data, a state-trait anxiety inventory, a scale of pre-disposing factors causing anxiety and an information questionnaire.Material and methodsAnxiety-predisposing factors and the influence of the information on the presence of anxiety were studied.ResultsHT patients: 47% had anxiety in the moment of the visit that was not related to the level of information received. The factor that worried them the most was the radioiodine administration. Being the first visit to a NMD significantly influenced (p<0.05) on the presence of anxiety.ResultsDTC patients: 42% had anxiety in the moment of the visit not related to the level of information received. The factor that worried them the most was the illness itself. No factor had a significant influence on the presence of anxiety.ResultsBC patients: 53% had anxiety in the moment of the visit that was not related to the level of information received. What worried them the most were the results. Having anxiety and/or depression significantly influenced (p<0.05) the presence of anxiety.ConclusionThe quantity of information given before a procedure in a NMD does not influence on the presence of anxiety. Nevertheless, it is our duty to give the best possible information(AU)

[Evaluation of the anxiety state in patients receiving radioiodine treatment or who undergo a sentinel lymph node examination in the Nuclear Medicine Department]. / Valoración del estado de ansiedad de los pacientes que reciben un tratamiento con radioyodo o son sometidos a una exploración de ganglio centinela en el servicio de Medicina Nuclear.

OBJECTIVE: To analyze the presence of anxiety in patients referred to a Nuclear Medicine Department (NMD). MATERIAL AND METHODS: A total of 148 patients were included: 67 were referred for radioiodine therapy, 48 with hyperthyroidism (HT), 19 with differentiated thyroid carcinoma (DTC), and 81 were referred for detection and biopsy of the sentinel node in breast cancer (BC). The following documents were filled out: personal data, a state-trait anxiety inventory, a scale of pre-disposing factors causing anxiety and an information questionnaire. Anxiety-predisposing factors and the influence of the information on the presence of anxiety were studied. RESULTS: HT patients: 47% had anxiety in the moment of the visit that was not related to the level of information received. The factor that worried them the most was the radioiodine administration. Being the first visit to a NMD significantly influenced (p<0.05) on the presence of anxiety. DTC patients: 42% had anxiety in the moment of the visit not related to the level of information received. The factor that worried them the most was the illness itself. No factor had a significant influence on the presence of anxiety. BC patients: 53% had anxiety in the moment of the visit that was not related to the level of information received. What worried them the most were the results. Having anxiety and/or depression significantly influenced (p<0.05) the presence of anxiety. CONCLUSION: The quantity of information given before a procedure in a NMD does not influence on the presence of anxiety. Nevertheless, it is our duty to give the best possible information.