Papillary thyroid carcinoma usually is sporadic, but may occur in a familial form. The complete clinical and pathological phenotype of familial papillary thyroid carcinoma (fPTC) has not been determined, and the susceptibility gene(s) is unknown. We investigated the clinical and pathological characteristics of an unusually large three-generation fPTC kindred to characterize more fully the clinical phenotype. We performed linkage analysis to determine the chromosomal location of a fPTC susceptibility gene. In addition to the known association of fPTC with nodular thyroid disease, we observed the otherwise rare entity of papillary renal neoplasia (PRN) in two kindred members, one affected with PTC and the other an obligate carrier. The multifocality of PRN in one subject adds weight to the likelihood of a true genetic predisposition to PRN. Both genetic linkage and sequence analysis excluded MET, the protooncogene of isolated familial PRN, as the cause of the fPTC/PRN phenotype. A genome-wide screening and an investigation of specific candidate genes demonstrated that the fPTC/PRN phenotype was linked to 1q21. A maximum three-point log of likelihood ratio score of 3.58 was observed for markers D1S2343 and D1S2345 and for markers D1S2343 and D1S305. Critical recombination events limited the region of linkage to approximately 20 cM. A distinct inherited tumor syndrome has been characterized as the familial association of papillary thyroid cancer, nodular thyroid disease, and papillary renal neoplasia. The predisposing gene in a large kindred with this syndrome has been mapped to 1q21.

We describe two Caucasian women with the concurrence of Graves' disease and the moyamoya phenomenon (radiological evidence of collateral cerebral blood vessels like "puffs of smoke" due to cerebrovascular occlusive disease). One patient presented with acute cerebrovascular ischemia due to Moyamoya disease shortly after radioactive iodine therapy for Graves' disease and the second presented with Graves' disease 10 years after being diagnosed with moyamoya dysplastic cerebral vessels. The optimal treatment of hyperthyroidism in these patients is unknown; however, careful control of the hyperthyroidism by any modality seems reasonable. Our limited experience suggests that antithyroid drugs and radioactive iodine therapy are rational options. Thyroidectomy appears to be a safe therapeutic alternative, although long-term efficacy may be difficult to assure. Both of our patients had to be treated twice for hyperthyroidism. Whether Graves' disease and Moyamoya coexist because of an aggressive autoimmune mechanism is a concept that remains to be settled.

Familial papillary thyroid carcinoma (fPTC) is an inherited tumor syndrome characterized by isolated papillary thyroid carcinoma (PTC) in affected subjects. Its etiology is unknown. Large multigeneration families with PTC are very rare, and therefore, modern genetic linkage studies have not been applied extensively to this disorder. Familial adenomatous polyposis coli (FAP) is an inherited tumor syndrome enriched in PTC. FAP is caused by germline mutations of the adenomatous polyposis coli (APC) gene that is located in the 5q21 region. It is not known if fPTC is a phenotypic variant of FAP, or if it is a genetically distinct disorder. We report a large 3-generation fPTC kindred and use linkage analysis to test the hypothesis that fPTC and FAP are genetically distinct. In this kindred there are 25 living informative subjects; 5 have PTC, and 1 is an obligate carrier. Inheritance is autosomal dominant with incomplete penetrance. There is vertical transmission, multifocal disease, an average age of onset of 36 years, and 1 subject has colon cancer. The probability is approximately 1 in 2 billion against the clustering of 5 sporadic PTC cases in this kindred. To test for linkage to the APC gene we used 2 highly polymorphic markers, D5S656 and D5S421, which are located within a maximum distance of 1.7 megabase (Mb) of the APC gene and within an estimated genetic region of less than 1 centimorgan (cM) from each other. After polymerase chain reaction (PCR) amplification 18 family members were genotyped. Construction and inspection of haplotypes showed that the affected subjects do not share the same allelic composition. Using a penetrance ratio of 75%, linkage was excluded at 2 cM and 3 cM on both sides of D5S656 and D5S421, respectively. The combined haplotype of these 2 markers provided an exclusion region of 4 cM. We conclude that fPTC is genetically distinct from FAP.

Hypertension can persist from pregnancy or present de novo in the postpartum period and continue to pose a risk to maternal well‐being. These risks are magnified as many patients present after hospital discharge and go unrecognized because of decreased medical surveillance after delivery. Guidelines for the management of postpartum hypertension are lacking, often resulting in imprecise diagnoses and incorrect treatment strategies. As hypertension specialists are called upon to provide advice to obstetricians regarding the management of hypertension in the postpartum period, it becomes important for the hypertension specialist to develop expertise in the evaluation and treatment of hypertensive women during the postpartum period. The purpose of this clinical review article is to provide an approach to the management of postpartum hypertension.

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