EFFECTS OF IODINE EXCESS ON THE THYROID
There are a number of effects on the thyroid of increasing levels of iodine. The following discussion is an attempt to summarize my (Zoë's) present understanding.
Intrathyroidal iodide level above critical threshold inhibits hormone synthesis.
When the iodide levels within the thyroid exceed a certain threshold, hormone production is inhibited.
Adaptation to iodide above above threshold requires from 26 to 50 hours.
About 48 hours after hormone production has been inhibited, the intrathyroidal iodide levels fall and hormone production returns to normal.
Excess intrathyroidal iodide inhibits iodide transport.
When the iodide levels within the thyroid get too high, it inhibits iodide transport into the cell. The iodide excess inhibits expression of the NIS gene, reducing the number of NIS transporters available to import iodide. This process allows the thyroid cell to regulate how much iodide is entering the cell and to maintain appropriate levels for hormone production.
Excess iodide may also be associated with a shorter half-life of the NIS.
The location of the expressed NIS seems a critical variable. Only the NIS located on the membrane can act as transporters. The iodide levels seem to affect how many of the NIS are located on the membrane.
Mechanisms for regulating intrathyroidal iodide can be impaired.
Sometimes the mechanisms for regulating intrathyroidal iodide can be impaired or defective. When this happens, the thyroid cells are not able to maintain optimal levels of iodide.
If inhibition continues longer than optimal, intrathyroidal iodide levels become too low and the effect of low iodide become apparent. On the other hand, if the intrathyroidal iodide becomes too high, other processes become involved.
Excess iodide inhibits TPO-catalyzed iodination.
Iodination is inhibited if iodide concentrations are greater than 1 mM. Excess iodide may also result in a decrease in TPO genetic expression.
Excess iodide inhibits cAMP formation.
Iodide decreases intracellular cAMP. This inhibitory mechanism may be responsible for the iodide-induced decrease in hormone secretion, amino acid and glucose uptake, protein biosynthesis, glucose oxidation, RNA biosynthesis, cell proliferation and thyroid growth in vivo. The cAMP pathway upregulates specific thyroid functions and differentiation.
Excess iodide inhibits the phosphatidyl inositol (PI) cascade.
Iodide inhibits the PI cascade. The PI cascade mediates thyroid cell proliferation, leading to dedifferentiation.
Excess iodide inhibits H2O2 generation.
Excess iodide inhibits thyroid growth.
Iodide inhibits thyroid cell proliferation. Derivatives of arachidonic acid participate in this process. The inhibitory effect of iodide and of delta-iodolactone on cell growth might be explained in part by an effect on the cAMP pathway. Both delta-iodolactone and omega-iodolactone cause a significant decrease in thyroid weight. Delta-iodolactone prevents goiter formation and produces involution of existing goiter.
Iodinated derivatives of arachidonic acid mediate effects of excess iodide.
Iodide dose required to induce inhibition varies.
The iodide dose required to trigger inhibition of hormone production varies based on the existing iodine status of the individual. For example, with iodine-deficient rats, a tiny dose (5-10 mcg) can trigger the inhibition. With iodine-sufficient rats, a much larger dose (50-100 mcg) is needed before the inhibition is triggered.
The level of iodide capable of inducing inhibition of organification (and, thus, thyroid hormone production) is determined by the ratio of organified to nonorganified intracellular iodide. This ratio depends on the previous iodide supply status.
Continual large doses of iodide create different conditions.
With large doses of iodide over a long period of time, more iodide is accumulated and organified (i.e., attached to the tyrosine in the Tg). However, the rate of secretion of T4 is not increased.
Instead, there is an increase in the release of noncalorigenic forms of iodine (e.g., forms other than T3 and T4). Most of the iodine lost from the gland is iodide (I-). This is referred to as the "Iodide Leak". The magnitude of the iodide leak varies directly with iodine intake.
Other inhibitory actions of excess iodide.
Iodide (and the many iodocompounds found in the thyroid) also affect many other processes within the thyroid gland. For example, there is evidence that the inhibitory actions of excess iodide include hormone secretion, thyroid blood flow, thyroglobulin proteolysis, glucose and amino acid transport, and protein and RNA biosynthesis, Na+/K+ ATPase activity, and the effects of TSH, EGF, IGF-1, insulin, and phorbol esters.
Very high doses of iodide inhibit most of the parameters of thyroid formation and growth.
