Hypothyroidism and Iodine Deficiency in an Infant Requiring Total Parenteral Nutrition

Iodine is an essential element for thyroid hormone synthesis. The thyroid gland has the capacity and holds the machinery to handle the iodine efficiently when the availability of iodine becomes scarce, as well as when iodine is available in excessive quantities. The latter situation is handled by the thyroid by acutely inhibiting the organification of iodine, the so-called acute Wolff-Chaikoff effect, by a mechanism not well understood 52 years after the original description. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones. The acute Wolff-Chaikoff effect lasts for few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns. This is achieved by decreasing the intrathyroidal inorganic iodine concentration by down regulation of the sodium iodine symporter (NIS) and therefore permits the TPO-H202 system to resume normal activity. However, in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues. Iodide-induced hypothyroidism has also been observed in patients with a history of postpartum thyroiditis, in euthyroid patients after a previous episode of subacute thyroiditis, and in patients treated with recombinant interferon-alpha who developed transient thyroid dysfunction during interferon-a treatment. The hypothyroidism is transient and thyroid function returns to normal in 2 to 3 weeks after iodide withdrawal, but transient T4 replacement therapy may be required in some patients. The patients who develop transient iodine-induced hypothyroidism must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Several mechanisms are involved in the maintenance of normal thyroid hormone secretion, even when iodine intake exceeds physiologic needs by a factor of 100. The sodium-iodide symporter system contributes most to this stability. Faced with an iodine excess, it throttles the transport of iodide into the thyroid cells, the rate-limiting step of hormone synthesis. Even before the iodine symporter reacts, a sudden iodine overload paradoxically blocks the second step of hormone synthesis, the organification of iodide. This so-called Wolff-Chaikoff effect requires a high (>or=10(-3) molar) intracellular concentration of iodide. The block does not last long, because after a while the sodium-iodide symporter shuts down; this allows intracellular iodide to drop below 10(-3) molar and the near-normal secretion to resume. In some susceptible individuals (e.g., after radio-iodine treatment of Graves' disease or in autoimmune thyroiditis), the sodium-iodide symporter fails to shut down, the intracellular concentration of iodide remains high and chronic hypothyroidism ensues. To complicate matters, iodine excess may also cause hyperthyroidism. The current explanation is that this happens in persons with goitres, for example, after long-standing iodine deficiency. These goitres may contain nodules carrying a somatic mutation that confers a 'constitutive' activation of the TSH receptor. Being no more under pituitary control, these nodules overproduce thyroid hormone and cause iodine-induced hyperthyroidism, when they are presented with sufficient iodine. These autonomous nodules gradually disappear from the population after iodine deficiency has been properly corrected. More recent studies suggest that chronic high iodine intake furthers classical thyroid autoimmunity (hypothyroidism and thyroiditis) and that iodine-induced hyperthyroidism may also have an autoimmune pathogenesis. Copyright 2009 Elsevier Ltd. All rights reserved.