Endemic Cretinism: Toward a Unifying Hypothesis

Abstract

Based on our data, the clinical picture of endemic cretinism results from the product of two pathophysiological events. Both events share a common feature, namely iodine deficiency, but act at different points in time. The first event occurs in all cretins and represents the prenatal action of thyroid hormone deficiency on brain development, transmitted vertically from mother to fetus, resulting in the neurological disorder of endemic cretinism. A consistent pattern and intensity of neurological, intellectual, and audiometric deficit is common to and equally present in all types of endemic cretin. The nature of these deficits points to an intrauterine insult to the developing fetal nervous system around the time of the midtrimester. The second event represents the postnatal action of thyroid hormone deficiency on somatic as well as brain development. Whereas previous workers had attributed the differences in the clinical presentation of endemic cretinism to the presence or absence of neurological features (i.e. prenatal hypothyroidism), the distinction between the types of endemic cretin can be related to the length and severity of postnatal thyroid hormone deficiency. Endemic cretins with predominant neurological features have had only transient hypothyroidism in the postnatal period, evidenced by their near normal thyroid function and by a lack of hypothyroid clinical features. By contrast, cretins with marked myxedematous features were characterized by permanent and severe postnatal thyroid hormone deficiency. These cretins, in addition to signs of neurological damage, were typically dwarfed, sexually immature, with marked clinical features of myxedema. This second event, influenced by the thyroid gland's morphologic response to its environment (goiter or thyroid atrophy), dictates the final clinical outcome. In conclusion, our hypothesis states that the clinical expression of endemic cretinism is determined by the sum of two pathophysiologic processes. The first process is fetal hypothyroidism which results in the neurological damage of the disorder and the second process is the duration and magnitude of postnatal hypothyroidism which dictates the final clinical appearance.

Endemic cretinism in Thailand: a multidisciplinary survey

“…Our study therefore supports the hypothesis that neurological defects, common to all types of cretins, are the result of the combination of maternal and fetal hypothyroxinemia secondary to iodine deficiency, whereas the degree of myxedematous features is due to the length and severity of postnatal hypothyroidism (6). Our study also indicates that the pathogenesis of endemic cretinism is universal and similar in different geographical areas of the world.…”

“…In contrast, restoration of thyroid function occurs postnatally in neurological cretins (6). The etiology of thyroid failure in myxedematous cretins remains speculative.…”

Thyroid ultrasound is the best prevalence indicator for assessment of iodine deficiency disorders: a study in rural/tribal schoolchildren from Gujarat (Western India)

“…Although the thyroid gland may become very enlarged it is not usually associated with morbidity. By contrast, the most damaging and pernicious effect of iodine de®ciency is on the developing brain, an effect mediated by perturbations to maternal and fetal thyroid hormone homeostasis (2). All iodine de®ciency disorders are preventable.…”

Apolipoprotein E is a genetic risk factor for fetal iodine deficiency disorder in China

“…This contrasts with the myxedemat-ous forms of cretinism whose severity depends upon the duration and magnitude of postnatal hypothyroidism, and is treatable to a large extent by postnatal thyroid hormone therapy. 6 Clinicopathological studies of FIDD are limited in number. Macroscopically the brain may be smaller than normal but is otherwise unremarkable.…”