Other Factors: Goitrogens and Metabolic Error

Western medicine, during the prophylactic era, understood iodine deficiency as the major cause of endemic goiter and cretinism. Since that era it has given increasing prominence to the role of goitrogens and metabolic error.

Goitrogens are any active forces or substances that induce goiter. They act in at least three ways, by affecting (1) the absorption of iodine into the bloodstream, (2) the chemical coupling of MITs and DITs to tyrosene, and (3) the binding of molecules. Goitrogens play an insignificant role in goiter and cretinism where the diet is varied, but where it is not (as in rural Asturias), they can play an extremely important role. In this chapter, I discuss only the goitrogenic mechanisms. In chapter 5, I will show how poverty induces a high goitrogen intake and how a selectively goitrogenous diet, for the physiological reasons given here, helps to keep segments of the population socially marginated.

Absorption is affected by thiocyanate, a substance produced either in the liver or intestine during the course of digesting foods from three plant families.^[12] Cassava is of the Euphorbiaceae (formerly Manihot) family, a starchy root widely consumed in the developing world. Cabbage, cauliflower, broccoli, rape seed, kale, collards, and turnips are of the Brassica family, and radish, cress, and mustard are members of the related Crucifera. Foods from these botanical groups are widely consumed in Europe and the temperate parts of the world, sometimes as garnishes and often as daily fare.

Thiocyanate produced by these goitrogenous foods preempts the sites on fatty acids to which iodine ordinarily binds for its passage through the intestinal membranes. Thiocyanate thus impedes the passage of iodine into the circulation and promotes its loss through feces. This loss is insignificant where iodine is abundant, but where it is scarce, thiocyanate slows down hormone production.

Perchlorate is another goitrogen acting in the same preemptive way in the intestine. While abundant in a variety of nuts, perchlorates are especially abundant in chestnuts (L. castanea sativa ), beechnuts, and acorns.^[13] In historical Europe, these nuts were considered "hungry foods," consumed as staples of daily fare only dur-

ing war or when grain crops failed. But as will be seen in chapters 5 and 7, they were regularly consumed where grain was habitually scarce.

Goitrins, another form of goitrogen, interfere with the coupling of MIT and DIT molecules. They too may be derived from cruciferous plants, more from turnips than from cabbage, becoming goitrins only in the presence of certain intestinal parasites that arise locally. They may also, as in one well-known case, be derived from volatile compounds of geologic origin. Where because of the prohibitive cost of fuel, only the richer segment of the population boiled its water, driving off these volatile compounds, only the poor became goitrous (Gait'án 1974). Goitrins like these pique the curiosity but play an insignificant role in the global distribution of endemic goiter and cretinism and contribute little to understanding the obstacles to prophylaxis.

Finally, there are mineral goitrogens that, absorbed through drinking water and passed into the bloodstream, act to bind iodine, thus making it less available for organification. The best-known mineral goitrogens are produced in groundwater flowing over bedrock of limestone, where minerals such as calcium and fluorine dissolve out of the rock, enter the water supply, and are ingested with drinking water. Mineral goitrogens like these are characteristic of the central Asturias and of the historical goiter belt of the American Midwest.

Hereditary metabolic error has come to assume, since midcentury, an increasing role in thyroidology and has become an important consideration in the diagnosis and management of goiter. Metabolic errors may impede iodine metabolism at several sites: they may impede the transport of iodine, the coupling and breakdown of molecules, and the recapture of iodine, leading in these several ways to symptoms like those produced by suboptimal iodine intake. While metabolic errors must be seriously considered in any idiopathic case of goiter or of other thyroid-related diseases, they have rarely been shown to play an important role in goiter and cretinism that is endemic. Even where the stage has been set for the concentration of metabolic error in inbred populations, iodine supplements have dramatically reduced the incidence of IDD. However, since popular interest in inbreeding outweighs popular interest in prevention, it serves the interest of the opponents of

prophylaxis to stir up renewed interest in inbreeding, thus distracting attention from prevention.

Supplementation

Determination of appropriate levels of iodine supplementation has frequently posed what might be considered a spurious problem for health officials deliberating over the institution of mass prophylaxis. This is largely because the breadth of the margin of optimal intake—as we saw in the dose response curve—has not been widely appreciated.

Even when mass prophylaxis was initially being tested, iodine supplementation gave generally satisfactory results. It was seen early on as preventing the appearance of goiter in the young; reducing diffuse, hyperplastic goiters; promoting the gestation and birth of normal offspring; and—once supplementation had been under way for the length of a gestation period—halting the addition of endemic cretins and congenitally deaf to the population. Goiters did not, however, recede in those cases where a stimulus to cell growth had been present over a long period.

In cases where goiter was well established and of long duration, supplementation was counterproductive, making some of the older women's hypertrophied glands tender and painful and threatening the possibility of recurring problems. This response made some physicians hesitate to introduce mass prophylaxis, for they feared inducing toxic goiter, an acute and life-threatening form of hyperthyroidism.^[14] As a result of such experience, guidelines were developed suggesting that iodine supplements be withheld from goitrous individuals over age forty. Such individuals could be supported with dessicated thyroid or with the synthetic thyroid hormone that became available after midcentury.

Supplementation posed other problems. Mistakes were made in the early prophylactic programs when very goitrous individuals were wrongly offered hope that their goiters would recede. When the goiters, unresponsive to supplementation, did not recede, their bearers were, on occasion, coerced into having them excised under primitive village conditions.^[15] It is understandable that women operated on so peremptorily might become apprehensive and resistant when large-scale prophylactic programs were later

undertaken. Memories of such interventions are passed down by word of mouth and produce psychological obstacles that, on the inauguration of new prophylactic campaigns, require sensitive management.^[16]

Prophylactic programs were originally aimed at eradicating only goiter and cretinism, since only these were understood as the acute and measurable manifestations of iodine deficiency. The conditions impeding vigor and cerebral function, surmised in those days but not amenable to quantification, were therefore not targeted for eradication. Medical men working in nonsupplemented areas where the incidence of endemic goiter was nevertheless declining measurably, wrongly came to assume that iodine intake was in the optimal range.^[17]

Under these circumstances, goiter and thyroid complaints that were brought to the clinic ceased to be viewed as responses to malnutrition. Instead, they came to be seen as "idiopathic" thyroid. At least in Asturias, therefore, thyroid disorders came to be managed surgically, pharmaceutically, or with radiation.^[18] But there is little reason to think these invasive practices were peculiar only to this region or to Spain. There is reason to think that, after the decline of endemic goiter in most of the Western world, enlargements of the thyroid came generally to be seen as idiopathic.^[19] The idea that, on a global scale, most thyroid disorders are preventable thus gradually faded away.^[20]