Evidence for interaction between the TCO and NMTC1 loci in familial non-medullary thyroid cancer.

BACKGROUND: Familial non-medullary thyroid cancer (fNMTC) is a complex genetic disorder that is more aggressive than its sporadic counterpart. Thus far, three genetic loci have been implicated in susceptibility to fNMTC by linkage analysis. METHODS: We used linkage analysis to test the significance of two of the known susceptibility loci for fNMTC, TCO on 19p13 and NMTC1 on 2q21 in 10 fNMTC families, nine of which present with cell oxyphilia, a rare histological phenotype associated with TCO. Furthermore, we used two-locus linkage analysis to examine the possibility that the TCO and NMTC1 loci interact to increase the risk of NMTC. RESULTS: The 10 families provided evidence for linkage at both TCO and NMTC, with LOD scores of 1.56 and 2.85, respectively. Two-locus linkage analysis, using a multiplicative risk model for the development of NMTC, achieved a maximum LOD of 3.92, with an LOD of 4.51 when assuming 70% of families were linked, indicating that the segregation in these families is consistent with an interaction model. Most of this evidence came from a large Tyrolean family that singularly achieved a two-locus LOD of 3.21. CONCLUSIONS: These results provide further evidence that susceptibility genes for fNMTC exist at 19p13 and 2q21, and furthermore, raise the possibility that in a subset of fNMTC pedigrees, these loci interact resulting in significantly increased risk of NMTC for patients that carry both susceptibility loci.

Surgical therapy for primary hyperparathyroidism in patients with previous thyroid surgery.

BACKGROUND: In patients with primary hyperparathyroidism (HPTH) and previous thyroid operations, complications of parathyroidectomy are more frequent than in patients undergoing initial neck surgery. The aim of this study was to investigate the value of preoperative imaging with regard to its influence on the surgical strategy. METHODS: We retrospectively analyzed 17 patients with primary HPTH and previous thyroid surgery. Preoperatively 16 patients underwent sonography and/or scintigraphy. RESULTS: Sonography had an overall accuracy to correctly localize enlarged parathyroid glands of 80%, and scintiscanning had overall accuracy of 78.6%. The accuracy of localization was increased up to 84.6% if both diagnostic procedures were applied. In patients with normal thyroid residues the accuracy of sonography was 85.7%, and it was 100% if scintiscanning was used. CONCLUSIONS: Preoperative localization techniques in patients with primary HPTH and previous thyroid surgery have high accuracy. This allows for an imaging-directed operative strategy, thus preventing unnecessary bilateral neck explorations, which carry a high risk of recurrent laryngeal nerve injury.

Management of hyperparathyroidism in an endemic goiter area.

In an endemic goiter area patients with hyperparathyroidism (HPTH) frequently also have thyroid abnormalities. In a retrospective study of 95 patients with HPTH we assessed the diagnostic accuracy of imaging techniques (ultrasonography or radionuclide scanning) for preoperative localization of parathyroid adenomas. Altogether 86% of our patients had goiter, requiring thyroid resections in 37%. For 19 patients the parathyroid exploration was the second or third cervical operation, most of them due to goiter. We found that the overall rate of transient and permanent recurrent nerve paralysis is considerably increased in patients with previous neck surgery (26% vs. 7%). The combination of ultrasonography and radionuclide scanning can lead surgeons to the site of parathyroid lesions responsible for HPTH in 85% of cases, although frequent nodular goiters can produce pitfalls for correct imaging in iodine-deficient countries. In endemic goiter areas preoperative localization studies can be recommended in patients with primary HPTH--for evaluation of thyroid pathology possibly leading to resection or its accuracy in localizing parathyroid adenomas. These studies also seem justified in patients with previously unsuccessful neck explorations for HPTH.

Thallium-201 gated single-photon emission tomography for the assessment of left ventricular ejection fraction and regional wall motion abnormalities in comparison with two-dimensional echocardiography.

Simultaneous assessment of myocardial perfusion and function by gated single-photon emission tomography (GS) after a single tracer injection provides incremental information and is feasible with technetium-99m sestamibi. The present study validated the use of GS with thallium-201 for the assessment of left ventricular ejection fraction (LVEF) and regional wall motion by comparison with two-dimensional (2D) echocardiography (echo), which has not been done before. After injection of 111 MBq 201Tl at peak bicycle exercise (n = 55) or pharmacological stress (n = 17), GS was acquired 15 (post stress) and 120 min post injection (rest) on a double-head camera. An automatic algorithm (QGS) was used for processing. Echo (Acuson Sequoia C256) was performed immediately after rest GS. LVEFs assessed by GS and echo were correlated. The overall and segmental sensitivity and specificity of GS for the detection of regional wall motion abnormalities (WMAs) were calculated, echo serving as the gold standard. Perfusion abnormalities were scored. The success rate of the automatic algorithm was 100%, and visually assessed image quality was good to excellent in 88% of cases. Post-stress and rest LVEF as assessed by GS were highly correlated (r = 0.91). Good correlations were obtained between post-stress LVEF (GS) and rest LVEF (echo) and between rest LVEF (GS) and rest LVEF (echo) (r = 0.76 and 0.86 respectively). In patients with a reduced LVEF of less than 50% (n = 23), these correlations were even better (r = 0.84 and 0.89 respectively). Regional wall motion abnormalities (WMAs) were identified by GS with high sensitivity and specificity (88%-100% and 82%-98% respectively) and were directly related to the extent and severity of stress as well as of resting perfusion defects. It is concluded that GS with 201Tl is a feasible and reliable tool for the evaluation of patients with compromised left ventricular function in the context of coronary artery disease, and thus improves diagnosis and prognostic stratification. Regional WMAs were identified with high diagnostic accuracy and the method may prove helpful for the detection of myocardial viability.