Alterations in Thyroid Blood Flow Induced by Varying Levels of Iodine Intake in the Rat*

Abstract

Thyroid hormone biosynthesis depends upon the presence of adequate amounts of thyroidal iodine, and during fluctuations in dietary iodine intake, relatively constant thyroid hormone levels are maintained by various homeostatic mechanisms. These mechanisms include an enhancement of iodide pump efficiency and organification when iodine intake is limited, and significant decreases in iodide uptake and hormone synthesis when excess iodine intake occurs. The present study was designed to determine whether acclimation to different dietary iodine regimens is associated with changes in thyroid blood flow and to assess the time course of any such alterations in relation to pituitary-thyroid axis hormone levels. Male Sprague-Dawley rats were fed a diet containing low (LID), high (HID), or normal (CTR) iodine concentrations. Three, 7, 14, or 133 days after starting these dietary regimens, the animals were anesthetized with ketamine/pentobarbital, and thyroid blood flows were assessed using the reference sample version of the microsphere technique. At the same times and at weekly intervals throughout the 133 days of treatment, blood samples for the determination of TSH, T4, and T3 levels were obtained. Additionally, thyroidal immunoreactive vasoactive intestinal peptide (VIP) was measured at the end of the experiments. LID treatment increased thyroid blood flows to 240%, 350%, and 240% of levels in control rats at 7, 14, and 133 days of treatment, respectively. Thyroid weight was also elevated above levels in control animals at each of these times. A slight decrease in plasma T4 levels occurred over the 133 days of LID treatment; however, this dietary regimen did not alter circulating levels of T3 or TSH or thyroidal VIP concentration. HID treatment had opposite effects, in general, to those of LID. Thyroid blood flows were decreased by 34%, 56%, 46%, and 35% after 3, 7, 14, and 133 days of treatment with HID, respectively. Circulating levels of T4 were increased over the 133 days of HID treatment, whereas plasma levels of T3 and TSH and thyroid weights remained unchanged from those in control rats over this period of study. A small decrease in thyroidal VIP concentrations coincident with the decrease in thyroid blood flow was observed at the beginning of the HID treatment. Neither LID nor HID had any effect on blood pressure, cardiac output, or blood flow in other organs. These data demonstrate that acclimation to changes in dietary iodine intake in the rat include alterations in thyroid blood flow which are reciprocal to the iodine intake level and appear to be independent of circulating TSH levels.

Iodine Deficiency Induces a Thyroid Stimulating Hormone-Independent Early Phase of Microvascular Reshaping in the Thyroid

“…Nevertheless, previous studies showed that changes in the thyroid blood flow can sometimes occur without any changes in TSH levels. 8,[32][33][34][35] Our results redefine these apparent discrepancies because they show that variations in the thyroid blood flow in response to goitrigen treatment occur in two distinct phases: an early phase that is completely TSH-independent and a second, later phase that is, in contrast, TSH-dependent. It should be noted that the early TSH-independent endothelial cell proliferation was originally reported more than 25 years ago, 4,5 without any satisfactory explanation having been given about the underlying mechanisms.…”

Doppler evaluation of the thyroid in pediatric goiter

“…In contrast, Arntzenius et al 6 found that marked changes in blood flow in the superior thyroid arteries of healthy, euthyroid subjects occurred during both low and high dietary intake of iodine and that serum thyrotropin levels remained within normal limits during the dietary change from low to high intake of iodine. Michalkiewicz et al 9 suggested that either some kind of neural stimulus to the vessels or locally generated paracrine substances cause the increases in thyroid blood flow during periods of iodine deficiency. We found no statistically significant correlation between the serum hormone profiles and Doppler parameters.…”

Relationships between cell division, expression of growth factors and microcirculation in the thyroids of Tg-A2aR transgenic mice and patients with Graves' disease

“…This is particularly true in the thyroid gland, where the microcirculation is extensively reformed during goitre formation and involution. Thus, in iodine-deficient goitres, the expansion of the vascular tree acts to prevent iodine shortage by enhancing clearance of iodine from thyrocytes (Wollman et al 1978, Denef et al 1989, Michalkiewicz et al 1989. Conversely, the vascular supply in iodine-induced goitre involution is promptly restricted in order to limit access of iodide to cells and the subsequent formation of toxic free radicals (Mahmoud et al 1986, Toussaint-Demylle et al 1990, Many et al 1992.…”