Thyroid morphology in lethal non-thyroidal illness: a post-mortem study

OBJECTIVE: Non-thyroidal illness (NTI) is associated with alterations in thyroid hormone metabolism. Whether morphological changes of the thyroid gland accompany NTI is unknown. The aim of the present study was to describe thyroid morphology in patients with lethal non-thyroidal disease. DESIGN: In an autopsy study 267 cases have been examined. METHODS: Clinical data were obtained from medical records. Subjects were patients with chronic disease (group A), intensive care patients (group B) or persons who had died suddenly without pre-existing illnesses (group C). Patients (n = 93) who did not fit into one of these categories and subjects with pre-existing thyroid disorders were excluded. Thyroid histology was assessed semi-quantitatively: grade I <25%, grade II 25--50% or grade III >75% occupation of the thyroid gland by follicles with a diameter <200 microm. RESULTS: Mean thyroid weight was 19.9 g in group A (n=75, age 19--96 (median 75) years, 48 males); 25.7 g in group B (n=64, age 24--93 (median 69) years, 43 males); and 26.0 g in group C (n=35, age 31--89 (median 69) years, 22 males) (P<0.0005, A vs B/C). Grade I thyroid histology was present in 6 out of 75 patients with chronic illness, in 3 out of 64 intensive care patients and in 33 out of 35 sudden-death subjects. Grade III thyroid histology occurred in 30 out of 75 chronically ill patients, in 17 out of 64 intensive care patients and in 0 out of 35 sudden-death subjects (P<0.0005, C vs A/B). CONCLUSIONS: NTI is associated with reduced thyroid follicular size that is accompanied by lower thyroid weight in chronically ill patients but not significantly in intensive care patients

FGFR3 and P53 characterize alternative genetic pathways in the pathogenesis of urothelial cell carcinoma

Fibroblast growth factor receptor 3 (FGFR3) and P53 mutations are frequently observed in bladder cancer. We here describe the distribution of FGFR3 mutations and P53 overexpression in 260 primary urothelial cell carcinomas. FGFR3 mutations were observed in 59% and P53 overexpression in 25%. Interestingly, FGFR3 and P53 alterations were mutually exclusive, because they coincided in only 5.7% of tumors. Consequently, we propose that they characterize two alternative genetic pathways in urothelial cell carcinoma pathogenesis. The genetic alterations were reflected in the pathology and the clinical outcome, i.e., FGFR3 mutations were found in low-stage/-grade tumors and were associated with a favorable disease course, whereas P53 alterations were tied to adverse disease parameters