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.