Long-lasting response to oral therapy in a young male with monogenic diabetes as part of HNF1B-related disease.

Mutations in hepatocyte nuclear factor 1ß gene (HNF1B) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations. LEARNING POINTS: HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history may not be present.Once diagnosis is made, treatment of diabetes with oral agents is worth trying, since the response can be sustained for a longer period than the one usually described. Oral treatment can help postpone insulinization and, once this is necessary, can help reduce the required doses.

Demografía, características clínicas y genéticas de pacientes con carcinoma medular de tiroides en los últimos 16 años en Castilla-La Mancha / Demographic, clinical, and genetic characteristics of patients with medullary thyroid cancer in the past 16 years in Castilla-La Mancha

OBJETIVO: El carcinoma medular de tiroides es un tumor de baja prevalencia cuyo pronóstico es peor que el del cáncer diferenciado de tiroides debido su mayor agresividad. El objetivo de este trabajo es describir las características demográficas, clínicas y genéticas de los pacientes atendidos en el área sanitaria de la Comunidad de Castilla-La Mancha durante 16 años. PACIENTES Y MÉTODOS: Los datos se recogieron mediante revisión de historias clínicas. RESULTADOS: Se revisaron las historias clínicas de 58 pacientes con una edad media al diagnóstico de 51 años (intervalo de 6 a 82 años) y un 63,8% de mujeres. La prevalencia fue de 2,84 casos por 100.000 habitantes, con una gran variabilidad entre áreas (de 0 a 5,4 casos por 100.000 habitantes). Los casos familiares representaron el 34,5% del total, siendo la mutación más frecuente la C634Y. El motivo más frecuente de diagnóstico fue la palpación de un bultoma cervical (70,6%); se solicitó ecografía al diagnóstico en 56 de 58 casos, y la calcitonina en 8 de 58 casos. La multicentricidad del tumor fue descrita en el 59 y 50% de los casos de síndrome de neoplasia endocrina múltiple tipo 2A y 2B, respectivamente, y en ningún caso esporádico. El 52% de los pacientes presentaba un estadio avanzado al diagnóstico (III o IV). La mediana de seguimiento fue de 36 meses (rango intercuartílico 14-210), con la pérdida de 11 pacientes durante el seguimiento. CONCLUSIONES: El diagnóstico de carcinoma medular de tiroides en Castilla-La Mancha se basa en la ecografía cervical, pero no en la calcitonina. Existe una alta prevalencia de este carcinoma, tanto familiar como esporádico, y una importante variabilidad en el tipo de mutación del protooncogén rearranged during transfection comparadas con las del resto de la población española

OBJECTIVE: Medullary thyroid cancer is a rare tumor that is more aggressive and has a worse prognosis than differentiated thyroid cancer. The purpose of this study was to report the demographic, clinical, and genetic characteristics of patients seen in the health care system of the community of Castilla-La Mancha over a 16-year period. PATIENTS AND METHODS: Data were collected through a review of patients' medical records. RESULTS: The medical records of 58 patients (mean age at diagnosis, 51 years; range, 6-82 years; 63.8% women) were reviewed. Prevalence rate was 2.84 cases per 100,000 inhabitants, with a high variability between areas (range, 0-5.4 cases per 100,000 inhabitants). Familial cases accounted for 34.5% of all medullary thyroid cancers, and the most common mutation was C634Y. The condition was most commonly diagnosed following palpation of a cervical lump (70.6%). At diagnosis, 56 of 58 patients underwent ultrasound and 8 of 58 patients were tested for serum calcitonin. Tumor multicentricity was reported in 59 and 50% of patients with multiple endocrine neoplasia syndrome type 2A and 2B, respectively, and in no sporadic cases. Fifty-two percent of patients had an advanced stage (III or IV) at diagnosis. Median follow-up was 36 months (interquartile range, 14-210); 11 patients were lost to follow-up. CONCLUSIONS: In Castilla-La Mancha, medullary thyroid cancer is diagnosed by cervical ultrasound, rather than calcitonin assay. There is a high prevalence of both familial and sporadic medullary thyroid cancer, and a significant variability in the type of proto-oncogen rearranged during transfection mutation as compared to the rest of the Spanish population

Demographic, clinical, and genetic characteristics of patients with medullary thyroid cancer in the past 16 years in Castilla-La Mancha.

OBJECTIVE: Medullary thyroid cancer is a rare tumor that is more aggressive and has a worse prognosis than differentiated thyroid cancer. The purpose of this study was to report the demographic, clinical, and genetic characteristics of patients seen in the health care system of the community of Castilla-La Mancha over a 16-year period. PATIENTS AND METHODS: Data were collected through a review of patients' medical records. RESULTS: The medical records of 58 patients (mean age at diagnosis, 51 years; range, 6-82 years; 63.8% women) were reviewed. Prevalence rate was 2.84 cases per 100,000 inhabitants, with a high variability between areas (range, 0-5.4 cases per 100,000 inhabitants). Familial cases accounted for 34.5% of all medullary thyroid cancers, and the most common mutation was C634Y. The condition was most commonly diagnosed following palpation of a cervical lump (70.6%). At diagnosis, 56 of 58 patients underwent ultrasound and 8 of 58 patients were tested for serum calcitonin. Tumor multicentricity was reported in 59 and 50% of patients with multiple endocrine neoplasia syndrome type 2A and 2B, respectively, and in no sporadic cases. Fifty-two percent of patients had an advanced stage (iii or iv) at diagnosis. Median follow-up was 36 months (interquartile range, 14-210); 11 patients were lost to follow-up. CONCLUSIONS: In Castilla-La Mancha, medullary thyroid cancer is diagnosed by cervical ultrasound, rather than calcitonin assay. There is a high prevalence of both familial and sporadic medullary thyroid cancer, and a significant variability in the type of proto-oncogen rearranged during transfection mutation as compared to the rest of the Spanish population.