Radioactive iodine in thyroid medicine

It has been known for about a century, that iodine is present in the thyroid gland and that iodine deficiency could induce goitre. During the 1930s the synthesis of radionuclids of iodine were initiated, enabling the characerization of thyroid iodine physiology. In 1946 two papers presented the initial use of radioactive iodine in the therapy of hyperthyroidism [1], [2]. Later the same year radioactive iodine was used to treat metastases of thyroid cancer [3]. This device was later introduced in Sweden by Jan Waldenström and Bengt Skanse. Today the use of radioactive iodine is the most common type of treatment in nuclear medicine. In Sweden almost 3000 treatments are given each year for thyrotoxicosis or thyroid cancer [4].

To recognize the use of isotopes a meeting entitled “Half a century with radioactive iodine in thyroid medicine – historical and future aspects” was arranged in Umeå in September 2005. The initiative to the meeting was taken by Professor Lars-Gunnar Larsson one of the pioneers in the field.

Mattsson and Johansson [5] presented the 36 different isotopes of iodine. The first isotopes used were ¹³⁰I and ¹³¹I. Today the most frequently used isotopes for morphologic diagnosis of the thyroid gland are ^99mTc, ¹²³I and ¹³¹I. There are still controversies to be solved concerning the optimal dosage of radioactive iodine in the treatment of hyperthyroidism. These are the determination of the volume of the functioning portion of the thyroid gland, the uptake, and the biological half-life of iodine.

The main risk factor for thyroid cancer is ionizing radiation. L-E Holm [6] reviewed the impact of exposure to ¹³¹I and thyroid cancer risk. Age at exposure is crucial and for those exposed during childhood the risk is considerably higher compared with those exposed during adult age. Several cohort studies on the use of radioactive iodine during diagnostic and therapeutic procedures indicate that the risk for persones exposed above the age of 20 years is limited. The consequences of the Chernobyl accident demonstrate the importance of iodine supplementation in the younger population [7]. This is probably the most powerful protective measure to prevent thyroid cancer. Not to mention endemic goitre and cretinism.

Lars-Gunnar Larsson presented some patients with functioning thyroid cancer treated at Radiumhemmet during the 1950s [8]. The patients were illustrated with scintigraphy showing the effect of therapy. One patient with slow progress of pulmonary metastases was treated with hypophysectomy. The effect of this operation on the pulmonary lesions was obvious.

In thyrotoxicosis iodine uptake by the thyroid gland is increased, a fact that facilitates treatment with radioactive iodine. However, for patients with thyroid cancer, means have to be taken to stimulate the uptake. Gertrud Berg [8] referred to different measures to optimize the use of radioactive iodine in the treatment of thyroid cancer, as an adjuvant to surgery or for patients with metastatic disease. The recent introduction of recombinant human TSH (rhTSH) has made the situation easier for the patients, who now can avoid the hypothyroid period during thyroid hormone withdrawal. A consensus report was recently published on the use of radioiodine as an adjuvant to surgery in differentiated thyroid cancer [9]. Reduced exposure to iodine prior to therapy is also of importance to reduce the risk of stunning.

The etiology of endocrine ophthalmopathy has long been unclear. Today the expression of TSH-receptor in the orbital tissue, and the presence of TSH-receptor antibodies may in part explain the ophthalmopathy in Graves’ disease. Anders Karlsson [10] showed that the endocrine ophthalmopathy is affected by the treatment given, with a higher risk for patients treated with radioactive iodine. To reduce to risk of eye complications it is important to minimize fluctuations of the thyroid hormone levels. High levels of thyrostatic drugs and corticosteroids are means to reduce the risk of endocrine ophthalmopathy in Graves’ disease.

The treatment alternatives for patients with non-toxic goitre were elucidated by Laszlo Hegedüs [11]. Surgery is recommended if the goitre compresses the trachea or the oesophagus, or if a malignant lesion is suspected. Radioactive iodine is another alternative, but with low uptake in the thyroid gland the activity given tends to be unnecessarily high. The use of rhTSH increases the efficacy considerably. The absorbed activity in the goitre is increased allowing the activity to be lowered. Furthermore, prestimulation decreases the extrathyroidal exposure. Caution must, however, be taken since swelling of the goiter and transient thyrotoxicosis may occur.

External ionizing radiation is a risk factor for primary hyperparathyroidism, most often caused by a parathyroid adenoma. A recent report on human exposure to radioactive iodine in young age in a region surrounding a nuclear site, showed no increased risk of hyperparathyroidism [12]. Rasmuson [13] analysed the incidence of parathyroid adenoma in a cohort of patients with thyrotoxicosis. In this cohort most of the patients had been treated with radioactive iodine, but no increase of the incidence of parathyroid adenoma was observed.