The major clinical and geographical differences, characteristic of the three distinct forms of endemic cretinism, are thought to be due to unique thyroid hormone imbalances. Neurological cretinism appears to reflect the negative impacts of severe foetal T4 deficiency, particularly during the second trimester. The dwarfism and mental retardation seen in Kaschin-Beck disease (grade III) may be caused by foetal and postnatal T3 inadequacy; whilst myxoedematous cretinism seems due to concurrent T4 and T3 defi-ciencies, especially during late foetal devel-opment and infancy.

Such thyroid hormone inadequacies can occur in a variety of ways, most commonly reflecting maternal diets deficient in iodine and/or selenium, which also may contain goitrogens and heavy metals. Excesses of iodine and possibly of selenium also appear capable of depressing both maternal and foetal thyroid hormone production.

This hypothesis, if correct, requires a reevaluation of both iodine deficiency disorder control programmes in areas of myxoedematous cretinism and of the treatment of congenital hypothyroidism. In both cases, iodine prophylaxis alone, whether as salt, oil or as L-thyroxine, will not prevent subse-quent developmental deficits if T3 deficiency is due to either selenium shortage or excess, or to a biochemical abnormality preventing the conversions of T4 to T3.