Thyroid Cancer and Precancerous Morbidity After Nuclear Fallout: Long-Term Cohort Study Near the Semipalatinsk Test Site

BACKGROUND: Populations living near the Semipalatinsk Nuclear Test Site (SNTS) in Kazakhstan were chronically exposed to low-to-moderate doses of ionizing radiation due to atmospheric nuclear testing (1949-1962). While the effects of acute exposures are well documented, data on long-term endocrine outcomes in chronically exposed adults remain limited. OBJECTIVE: To evaluate thyroid and metabolic morbidity and its association with reconstructed radiation dose in a long-term adult cohort exposed to fallout. METHODS: This cohort study included 3,240 individuals who underwent thyroid ultrasound screening between 1998 and 2002. Thyroid doses were reconstructed individually using a fallout-specific dosimetric model based on age, diet, and geographic location across 125 nuclear tests. Endocrine outcomes were assessed through ICD-10 diagnoses and follow-up surveys in 2023-2024. Associations between dose and endocrine morbidity were analyzed using logistic regression, adjusted for sex, age at exposure, smoking, obesity, parity, and hormone therapy. RESULTS: By 2024, 1,099 individuals (33.9%) were alive. Among them, 63% reported thyroid disease, 33% had received hormone therapy, and 2% had undergone surgery. Verified endocrine diagnoses were identified in 712 individuals (21.9%), including non-toxic diffuse goiter (28.1%), multinodular goiter (19.5%), and single nodular goiter (7.9%). Thyroid dose was positively associated with endocrine morbidity (OR = 1.42; 95% CI: 1.22-1.65; p < 0.001). Female sex, early exposure, obesity, and smoking were also significant predictors. CONCLUSIONS: Decades after fallout exposure, thyroid and metabolic disorders remain prevalent in affected populations. The findings support continued endocrine surveillance and provide robust evidence of a dose-dependent endocrine risk in adults exposed to environmental radiation.