Recent advances in protein metabolism and in glycoprotein synthesis bring futher insight into endemic goiter epidemiology. Retinol circulates in the blood stream in close parallelism with retinol-binding protein and prealbumin (RBP-PA), a protein complex whose liver secretory rate is dependent upon hormonal and nutritional status. On the other hand, normal glycosylation reaction occurs through the formation of a retinol-linked sugar complex. It is suggested that the relative drop of serum retinol levels, as a result of modified hormonal climate and/or declining protein status, might constitute a critical factor capable of inducing a defective incorporation of mannose into native thyroglobulin, leading to an early depression of the full glycoprotein production. This concept affords a comprehensive explanation of the following unresolved data recorded in goitrous areas: (1) clinical and biochemical discrepancies between subjects living in the same morbid territory, (2) persistence of endemicity in spite of appropriate iodine supplementation, (3) similar prevalence of goiter hypertrophy in male and female prepubertal children, (4) increased frequency of goiter enlargement in the four most vulnerable groups, namely preschool children of both sexes, adolescent girls, pregnant women, and elderly persons, (5) decreased impact of thyroid swelling accompanying improved socio-economic status, even without iodine addition, and (6) resurgence of goitrous hyperplasia as an effect of seasonal or sporadic deterioration of nutritional habits, even when iodine supply remains unchanged. © 1979.