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Delange, Thilly
Goitrogenic FactorsDelange FM from "Iodine Deficiency" in Braverman & Utiger, The Thyroid, 8th edition, 2000, p 298.
"Iodine deficiency is not the sole cause of endemic goiter. Indeed, the disease has been found in regions where there is no iodine deficiency or even iodine excess. Conversely, in other regions with an extremely severe iodine deficiency, endemic goiter is not observed. These data strongly suggest that some goitrogenic factors in the diet or environment, other than iodine deficiency, could play a critical role in the etiology of the disease….
"Natural goitrogens were first found in vegetables of the genus Brassica (the Cruciferae family), which possesses goitrogenic properties in animals. Their antithyroid action is related to the presence of thioglucosides, which, after digestion, release thiocyanate and isothiocyanates. A particular thioglucoside, goitrin (L-5-vinyl-2-thiooxazolidone) is present in certain Cruciferae growing as weeds in pastures in Finland and Tasmania. Goitrin has potent thionamide-like properties. Goitrin in humans could probably be ingested from milk.
"Another important group of naturally occurring goitrogens is the cyanoglucosides, which have been found in several staples (cassava, maize, bamboo shoots, sweet potatoes, lima beans). After ingestion, these glucosides release cyanide, which is detoxified by conversion to thiocyanate, a powerful goitrogenic agent that acts acutely by inhibiting thyroid iodide transport and at higher doses, competes with iodide in the organification processes."
Iodine deficiency, other trace elements, and goitrogenic factors in the etiopathogeny of iodine deficiency disorders (IDD).Thilly CH, Vanderpas JB, Bebe N, Ntambue K, Contempre B, Swennen B, Moreno-Reyes R, Bourdoux P, Delange F. Biol Trace Elem Res. 1992 Jan-Mar;32:229-43. [abstract only]
"Severe goiter,
cretinism, and the other iodine deficiency disorders (IDD) have
their main cause in the lack of availability of iodine from the
soil linked to a severe limitation of food exchanges. Apart from
the degrees of severity of the iodine deficiency, the frequencies
and symptomatologies of cretinism and the other IDD are
influenced by other goitrogenic factors and trace elements.
Thiocyanate overload originating from consumption of poorly
detoxified cassava is such that this goitrogenic factor
aggravates a relative or a severe iodine deficiency. Very
recently, a severe selenium deficiency has also been associated
with IDD in the human population, whereas in animals, it has been
proven to play a role in thyroid function either through a
thyroidal or extrathyroidal mechanism. The former involves
oxidative damages mediated by free radicals, whereas the latter
implies an inhibition of the deiodinase responsible for the
utilization of T4 into T3. One concludes that: 1. Goiter has a
multifactorial origin; 2. IDD are an important public health
problem; and 3. IDD are a good model to study the effects of
other trace elements whose actions in many human metabolisms have
been somewhat underestimated."
[Excess of thiocyanate and selenium deficiency: cofactors in the etiology of endemic goiter and cretinism in North Zaire]Thilly CH, Contempre B, Vanderpas JB. Bull Mem Acad R Med Belg. 1990;145(11):440-8; discussion 448-50. French. [abstract only]
"Endemic goitre is accompanied by a spectrum of iodine deficiency disorders (IDD). From work undertaken by CEMUBAC in Ubangui Zaire, the role of thiocyanate overload is recalled while this work demonstrates for the first time in man an action of selenium supplementation (and thus deficiency) on thyroid function in iodine deficient areas. The extreme severity of the selenium deficiency may intervene either on the central and/or peripheral deiodination of thyroxine, or on the synthesis of the thyroid hormones. Together with thiocyanate overload, selenium deficiency may be responsible of the high frequency of myxedematous cretins in Zaire."
Cassava and the thyroidDelange F Chapter 13 in Environmental Goitrogenesis by E Gaitan, 1989, pp 173 - 194.
"SCN [thiocyanate] inhibits the trapping of iodide by the mammary gland. This at least partly explains the extremely low content of iodine found in breast milk in the Ubangi area in Zaire.... In contrast, thiocyanate freely crosses the placenta and there is a direct relationship between the serum concentrations of thiocyanate in mothers at delivery and in cord blood."
"Conclusions. Cassava is a potential goitrogenic agent. Thiocyanate is the goitrogenic factor directly involved. Thiocyanate results from the endogenous conversion of cyanide released from cassava by the hydrolysis of linamarin, its main cyanogenic glucoside.
"The effects of thiocyanate mimic entirely the ones of iodine deficiency. For this reason: (1) it is particularly difficult to distinguish the specific role of iodine deficiency and SCN overload; (2) SCN overload has goitrogenic properties only when the iodine supply is low; and (3) the goitrogenic action of cassava can be entirely corrected by increasing the supply of iodine.
"Several factors are involved in the goitrogenic action of cassava: (1) the SCN content of fresh cassava; (2) the efficiency of the detoxification processes used during the preparation of cassava-based foods; (3) the frequency and quantity of consumption of these foods; and finally (4) the level of iodine intake in the diet.
"It has been established that the goitrogenic action of cassava is critically related to the balance between the dietary intakes of iodine and SCN. This balance can be estimated for public health purposes by the man urinary iodine/SCN ratio (mcg/mg) obtained in unselected and representative samples of the population: under normal conditions, this ratio is above 7; endemic goiter develops when it reaches the critical threshold of 3 and becomes hyperendemic, complicated by cretinism, when it is lower than 2.
"Because of the several factors determining the value of this ratio, there will not necessarily be a superimposition between cassava consumption and endemic goiter; this will occur only when the critical threshold I/SCN will be reached. A limiting factor to the relationship between this ratio and the prevalence of goiter could be the protein supply. The possibility arises that in the presence of protein malnutrition, the development of goiter in the presence of SCN overload will be impaired while the yield of synthesis of thyroid hormones will be affected; in this situation, the prevalence of goiter will underestimate the antithyroid action of cassava. Finally, in conditions of extreme malnutrition where the supply of sulfur will limit the conversion of cyanide into thiocyanate, the toxicity of cassava will result from cyanide poisoning and will affect the nervous system and will no longer result from SCN affecting the thyroid gland.
"Because of the similarity of the antithyroid action of both iodine deficiency and SCN overload, and because these two conditions are not rarely associated, the specific role of cassava in the etiology of endemic goiter is possibly underestimated on a world scale at the present time. It could be considered that, except for its scientific interest, this underevaluation is of no practical importance for public health purposes. It is probably not meaningless, however, to be aware of this situation because there is the risk that, due to limitations in food supply in more and more tropical and subtropical areas in the world in the future, increasing consumption of cassava in populations with a borderline iodine supply could precipitate the occurrence of endemic goiter in so far unaffected populations."
[The role of goitrogenic factors distinct from iodine deficiency in the etiology of goiter]Delange F. Ann Endocrinol (Paris). 1988;49(4-5):302-5. Review. French. [abstract only]
"The main cause of endemic and sporadic goiter is a deficiency in the dietary supply of iodine. However, iodine deficiency is not the only cause of goiter. This paper reviews present knowledge on the role of naturally occurring goitrogens in the etiology of goiter. Vegetables from the Cruciferae family, chronic consumption of poorly detoxified cassava containing large amounts of cyanogenic glucosides, flavonoids, humic substances originating from the organic residues in the soil are clearly involved in the etiology of endemic goiter. Iodine excess, especially in the newborn infants, lithium and thiocyanate overload resulting from smoking habits can be responsible for the development of goiter in non endemic areas."
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