Hypothyroxinemia, iodine deficiency, and subtle changes in migration and cytoarchitecture.

In the Guest Editorial in the September issue of EHP, Zoeller (2003) commented on an article by Lavado-Autric et al. (2003). Lavado-Autric et al. (2003) used the term "hypothyroxinemia" in this article to indicate that thyroxine ([T.sub.4]) or free [T.sub.4] concentrations are low compared with values usually found at the same stage of pregnancy in normal women with adequate iodine intake, with or without the presence of clinical or subclinical hypothyroidism (when thyroid-stimulating hormone is above normal values). This is important because, in many instances, women in iodine-deficient populations are hypothyroxinemic; these women are not clinically hypothyroidal because they have normal or above-normal levels of circulating 3,5,3'-triiodothyronine ([T.sub.3]) that can be supplied to the tissues.

It is important to note that the rats in the study were treated drastically by Lavado-Autric et al. (2003). The dams were first fed a diet with a low iodine content (LID) for 10 days and given an incredibly high amount of a goitrogen--1% perchlorate (KCI[O.sub.4])--in the drinking water re lower the initial content of iodine-containing compounds in the thyroid gland; the 1% KCI[O.sub.4] was then withdrawn. After dividing the rats into three groups, Lavado-Autric et al. (2003) treated one group with LID containing potassium iodide (LID-plus-KI) to ensure a normal iodine intake (approximately 10 [micro]g iodine/day), the second group with LID alone (LID-1), and the third group with LID containing 0.005% KCI[O.sub.4] (LID-2). This third treatment was used to further decrease thyroid uptake of the small amounts of iodine contained in the LID itself and in the supplements given to the rats throughout pregnancy and lactation to prevent nutritional deficiencies other than iodine.

In his editorial, Zoeller (2003) stated the following:

   Lavado-Autric et at. (2003) reported that subtle
   TH [thyroid hormone] insufficiency in the pregnant
   rat disrupts the migration of neurons in the
   fetal cortex and hippocampus....

This was not subtle TH insufficiency. In fact, Lavado-Autric et al. (2003) stated that

   [T.sub.4] values in the LID-1 dams were well below
   normal (< 10% of the values of LID-plus-KI
   dams), and [T.sub.3] values remained normal, in LID-2
   dams, however, [T.sub.3] values decreased, though
   much less markedly than [T.sub.4]. Despite the decrease
   in [T.sub.3] values, the reproductive performance of
   these animals was normal, as was the postnatal
   growth of the pups at [postnatal day 40].

As a result,

   the subtle changes in cytoarchitectonic organization
   found in the progeny of both LID-1 and
   LID-2 darns indicate that the normal process of
   brain maturation ... [is] likely to be impaired.

The author declares he has no competing financial interests.

Offie P. Soldin

Lombardi Cancer Center

Georgetown University Medical Center

Washington, DC

E-mail: [e-mail]

REFERENCES

Lavado-Autric R, Auso A, Garcia-Velasco JV, Arufe Mdel C, Escobar del Rey F, Bethel P, et al. 2003. Early maternal hypothyroxinemia alters histogenesis and cerebral cortex cytoarchitecture of the progeny. J Clin Invest 111(7):1073-1082.

Zoeller RT. 2003. Thyroid toxicology and brain development: should we think differently? [Editorial]. Environ Health Perspect 111:A628.