Familial pituitary adenomas with a heterogeneous functional pattern: clinical and genetic features.

Familial pituitary adenoma is a rare syndrome which may present either as isolated lesions, or in association with other endocrine tumors, for example in the frame of multiple endocrine neoplasia (MEN-1) or Carney complex (CNC). The most frequently described forms of familial isolated pituitary adenoma (FIPA) are familial somatotropinomas or prolactinomas. Recently, some cases of familial isolated somatotropinoma have been associated with germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene. The present report shows heterogeneous FIPA with 3 subtypes of tumor in 3 individuals of the same family: somatotropinoma in the proband, giant prolactinoma in a brother, and gonadotroph cell macroadenoma in the father. A prospective survey also suggested the occurrence of a silent microadenoma in the proband's sister. Clinical screening was performed in the 3 affected members, the 4th suspected case, and 9 additional, asymptomatic relatives. They had no clinical evidence of associated endocrine lesion suggesting MEN-1 or CNC. Genetic screening for germline mutation of the MEN-1, the gene encoding the protein kinase A (PKA) type 1 alpha regulatory subunit (R1 alpha) (PRKAR1alpha) and AIP gene was negative in 2 affected members. In conclusion, these data suggest that familial pituitary adenomas can occur with a heterogeneous functional pattern that is distinguished from MEN-1 or CNC. The absence of mutation of the recently described AIP gene suggests the implication of other predisposing gene(s). Collaborative, multicentric studies are needed to further define the location of gene(s) involved in heterogeneous FIPA.

Familial aggregation of LADA and juvenile type 1 diabetes in a French Caucasian family.

We describe here the unusual aggregation of diabetes cases in a family of 10 subjects. Among them, three adult siblings presented with LADA and one child presented with juvenile type 1 diabetes. Although the exact pathogenesis of LADA is unknown and questions the role of autoimmunity in beta cell failure, the familial aggregation of these two forms of diabetes underlines the existence of common roots, i.e. immune mechanisms and genetic susceptibility. This report clearly illustrates the differences in terms of autoimmunity (prevalence and titer of GAD and IA2 antibodies) and HLA class II genotype between patients with LADA and those with juvenile type 1 diabetes.

Hürthle cell thyroid carcinoma metastatic to the sigmoid colon.

Prognosis of differentiated thyroid cancer is favorable in the majority of cases. However, distant metastases occur in 10-15% of cases, predominantly in lungs and bones, especially in older patients exhibiting poorly differentiated forms or advanced stages. We report a case history of Hürthle cell thyroid carcinoma metastasized to the sigmoid colon. To the best of our knowledge, this location has never been described before. This case history illustrates the difficulties of diagnosis and treatment in patients whose metastases do not concentrate radioiodine. The interest of different imaging modalities, including fluoro-deoxy-glucose positron emission tomography scan and somatostatin receptor scintigraphy, is discussed.