RESUMEN
BACKGROUND: The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the Pendred's syndrome (PDS) gene that encodes pendrin, a chloride/iodide transporter expressed in the thyroid, the inner ear, and the kidney. OBJECTIVE: To perform a detailed clinical and molecular analysis of patients with Pendred's syndrome from four patients from three unrelated Mexican families. METHODS: Thyroid function tests, perchlorate test, thyroid scintigraphy, audiometry, computer tomography and magnetic resonance imaging were performed in all affected individuals. Haplotype analyses were performed using microsatellite markers flanking the PDS locus, and the PDS gene was submitted to direct sequence analysis. RESULTS: All patients presented with sensorineural deafness, Mondini malformations of the cochlea, an enlarged vestibular aqueduct, goiter, and a positive perchlorate test. Two patients were hypothyroid, two individuals were euthyroid. Sequence analysis revealed a complex homozygous deletion/insertion mutation at the end of exon 4 in the index patient of family 1 resulting in a premature stop codon at position 138. In family 2, the affected individuals were compound heterozygous for a splice acceptor mutation (IVS2 -1G>A) and a 1231G>C transversion substituting alanine 411 by proline (A411P). In family 3, the index patient was found to be homozygous for a transversion 412G>T in exon 4 replacing valine 138 by phenylalanine (V138F). CONCLUSIONS: All patients included in this study presented with the classic Pendred syndrome triad and molecular analysis revealed pendrin mutations as the underlying cause. The identification of three novel mutations, one of them of complex structure, expands the spectrum of mutations in the PDS gene and emphasizes that they display marked allelic heterogeneity.
Asunto(s)
Bocio/genética , Pérdida Auditiva Sensorineural/genética , Yoduros/metabolismo , Errores Innatos del Metabolismo/metabolismo , Adolescente , Niño , Femenino , Haplotipos , Humanos , Yodo/sangre , Imagen por Resonancia Magnética , Masculino , Mutación/genética , Linaje , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Síndrome , Hormonas Tiroideas/sangre , Tomografía Computarizada por Rayos XRESUMEN
An unusual presentation of periodic paralysis in a Mexican man with thyrotoxicosis is presented. The patient suffered paralysis of the lower extremities without apparent precipitating factors such as hypokalemia, exercise, carbohydrate or alcohol ingestion. Hyperthyroidism was managed first with a thyroid suppressant (methimazole) and propranolol. Prednisone was added after another episode of paralysis. Definitive treatment of hyperthyroidism was achieved with radioactive iodine, which subsequently required substitution therapy with thyroxine. A moderate dose of thyroxine (100 microg) caused muscular weakness. Treatment of thyrotoxicosis and flaccid paralysis as well as the effects of glucocorticoids on thyroid function are discussed.
Asunto(s)
Parálisis/tratamiento farmacológico , Potasio/sangre , Tirotoxicosis/tratamiento farmacológico , Adulto , Quimioterapia Combinada , Humanos , Masculino , Metimazol/uso terapéutico , Parálisis/etiología , Prednisona/uso terapéutico , Propranolol/uso terapéutico , Recurrencia , Pruebas de Función de la Tiroides , Tirotoxicosis/sangre , Tirotoxicosis/complicaciones , Tirotoxicosis/diagnóstico , Tiroxina/uso terapéuticoRESUMEN
We present a prospective study of 88 patients with thyroid nodules seen in our institution in 1985-86 and the results of a 5 year follow up. The algorithm for resolution among different therapeutic options was established in regard to the clinical characteristics, imaging and particularly the histopathologic studies. Their age ranged from 18 to 79 years; 94% of the patients were females. Most of the nodules were solid (69%) and measured 1-4 cm in diameter. The image of 62% of the thyroid scans was of a non-functioning nodule and 13% were hyperfunctioning. In 80% the ultrasonographic pattern was solid or mixed. Surgery was undertaken in 19 patients (21%). In 58%, a diagnosis of malignancy was established. The biopsy (aspiration and tru-cut) suggested the presence of the malignant tumors when taken together in 90% of the cases. Hormonal treatment was given to 62 patients; in 40-45% of them there was a significant reduction in the size of the nodule. Aspiration and sclerosis of cystic nodules were performed in 19 patients with significant shrinkage in 82%. Radioactive iodine was used in 11 patients. Our algorithm reduces costs and precludes unnecessary morbidity in patients with thyroid nodules.