Radioiodine Therapy: Effects

Radioiodine therapy (RJT; also radioiodine therapy, RIT) is one of the nuclear medicine procedures in which open radionuclides are used to treat various benign and malignant diseases. A radionuclide is a nuclide (atomic species with specific mass number, i.e., based on the number of nucleons (protons and neutrons) and atomic number, i.e., based on the number of protons) with radioactive properties. Radioactive nuclides have free energy, which they can transmit in the form of alpha, beta or gamma rays. These three types of radiation are also called ionizing radiation because their energy is sufficient to remove electrons from their regular position in the atomic shell, thus turning the atom into an ion (electrically charged atom). Ionization alters chemical properties of atoms and molecules, and the hereditary subtance of cells (DNA) is particularly susceptible to such radiation. In the case of high-grade radiation damage and failure of the cell’s own repair mechanisms, apoptosis (programmed cell death) ultimately occurs. Such cell damage is desired, for example, in tumor cells in therapy with radionuclides. However, healthy body cells should be spared as much as possible. In radioiodine therapy, the radioactive iodine nuclide 131J is used. Since functioning thyroid tissue or thyroid tumors require iodine to maintain their metabolism, the administered 131J is supplied to the organ or tumor via the bloodstream and enriched there. The therapeutic effect is caused almost exclusively by the beta radiation of the 131J. This leads to irreversible cell damage, so that excessively active or malignant degenerated thyroid tissue is eliminated. The success rate of radioiodine therapy is about 90%. Thyroid volume decreases by approximately 20 ml during therapy.

Indications (areas of application)

Radioiodine therapy is an effective therapeutic procedure that should always be considered as an alternative to surgery for benign (benign) thyroid disease. Radioiodine therapy is particularly preferable when functional symptoms are the primary concern and mechanical impairment, such as compression (narrowing) of the trachea by goiter (thyroid enlargement), is in the background.

  • Hyperthyroidism (hyperthyroidism).
  • Autonomous adenoma of the thyroid gland (nodular tissue that independently produces thyroid hormones independently of the hormonal control circuit and can therefore lead to hyperthyroidism)
  • Nodal goiter with small or large thyroid volume.
  • Small or medium-sized goiter in Graves’ disease.
  • Large and very large goiter (goiter; a palpable, visible or measurable enlargement of the thyroid gland) (volumes 100-300 ml): especially in the elderly, as well as in patients with concomitant diseases, where surgery should be avoided if possible, a goiter can be reduced by radioiodine treatment.
  • Previous surgery on the thyroid gland, recurrent paresis (vocal cord paralysis).
  • Temporary postoperative hypoparathyroidism (parathyroid hypofunction) after initial surgery.
  • Refusal of surgery
  • Increased risk of surgery

Radioiodine therapy is also possible in mild endocrine orbitopathy (eye involvement; immunologically induced inflammation of the orbital contents). In thyroid carcinoma (thyroid cancer), radioiodine therapy is indicated following total surgical thyroidectomy (thyroidectomy). Before therapy, intact thyroid tissue should always be completely removed, since carcinoma tissue stores radioiodine to a lesser extent and thus sufficient accumulation in residual tumor tissue, recurrences (recurrent disease), or metastases (daughter tumors) would not be achieved. Well-differentiated thyroid carcinomas (papillary or follicular thyroid carcinoma) are suitable; medullary (C-cell carcinoma; MTC) or anaplastic thyroid carcinomas do not provide an indication because of insufficient iodine storage capacity.

Contraindications

  • Gravidity (pregnancy)
  • Suspected malignancy (malignancy): in the case of carcinomas, surgical removal including histological (fine tissue) examination is always required beforehand.
  • Goiter with pronounced mechanical symptoms: In the case of high-grade constriction of the surrounding structures (eg.B. Trachea), only a small swelling of the thyroid gland in the context of radiation (radiation thyroiditis) can lead to dangerous obstruction (occlusion).
  • Large strumen with cysts or cold (here: metabolically inactive) nodules: These areas are not amenable to radioiodine therapy due to poor 131J storage.

Before the examination

Before performing radioiodine therapy, it is necessary to calculate the dose of therapy. Depending on the size of the organ as well as metabolic activity of the thyroid gland, a different part of the applied (administered) 131J actually arrives at the desired location. Thus, the therapeutic dose is individual and is determined by the following parameters:

  • Thyroid mass: determination by sonography (ultrasound), scintigraphy and palpation findings (palpation findings).
  • Effective half-life: a radioiodine test is performed. This involves determining the activity of the thyroid gland by measuring the percentage of radioiodine uptake after 24, 48, and 72 h. For convenience, standardized tables or formulas can also be used, which require only a single measurement, but are also less accurate.

The required therapy activity must then be calculated accurately. For this purpose, for example, the Marinelli formula can be used. In addition, oral and written patient education about the radiation protection measures to be observed is required by law.

The procedure

In Germany, the patient is admitted as an inpatient. The radioactive iodine isotope iodine-131 (131J) can be administered in liquid form or as a capsule.

  • Peroral (by mouth) application (administration): the patient receives the radioiodine in a lead container with a drinking straw and must drink water afterward. An alternative is gelatin capsules, which can be swallowed like tablets and offer the advantage of less risk of contamination.
  • Intravenous application: radioiodine can also be infused (infusion) directly into the vein through a cannula.

The radiation effect of the 131J consists of 95% beta rays. These beams have a mean range of 0.5 mm and maximum range of about 2 mm. This allows very precise irradiation of the desired regions while sparing the surrounding structures (selective therapy). Gamma rays account for 5% of the total radiation and are used to quantify the localization of the 131J from the outside (scintigraphy). Thus, it can be estimated at which site the beta rays are therapeutically effective. Depending on the dose of radiation administered, two therapeutic approaches are distinguished in the treatment of benign thyroid lesions:

  1. Ablative radioiodine therapy: higher activity is deliberately applied and the therapeutic goal is hypothyroidism (hypothyroidism). This can be subsequently compensated with thyroid hormones.
  2. Function-optimized dose: the goal is to achieve or maintain euthyroidism (normal thyroid metabolism).
    • Efficient volume reduction in large and very large volumes (volumes 100-300 ml) by about 35-40% after one year, about 40-60% after two years.

In postoperative therapy of thyroid carcinoma, a distinction is made between ablation (removal) of the residual thyroid gland about 3-4 weeks after surgery and targeted therapy of recurrence or metastasis when needed.

After the examination

  • Patients remain inpatients for at least 48 h in a nuclear medicine ward with special wastewater collection facilities, since radionuclides are excreted through the kidney in the urine and cannot be added to the environment in active form.
  • During the inpatient stay, posttherapy dosimetry provides the opportunity to determine the actual focal dose. If a dose deficit is found, additional radioiodine therapy may be indicated (necessary) after a few days.
  • Despite discharge from the hospital, precautions must continue to be taken for 1-2 weeks: Patients should keep their distance from young children and pregnant women, and also avoid social venues (such as the cinema or theater).
  • Hyperthyroidism is usually eliminated after two to six months after radioiodine therapy.
  • Control of metabolic status should be carried out at short-term intervals of two to three weeks, for example, in Graves’ disease to be able to reduce thyrostatic medication in time and initiate substitution therapy with levothyroxine in time.
  • There must be regular follow-up examinations with control of thyroid parameters (TSH, fT3 and fT4). Especially in ablative radioiodine therapy, hypothyroidism therapy (1.6 µg/kg body weight levothyroxine) must be adjusted correctly (annual control).

Possible complications

  • Struma swelling (possible early effect).
  • Radiation thyroiditis: radiation-induced thyroiditis may occur 2-4 days after therapy (symptoms: swelling of the thyroid gland, pressure pain in the thyroid bed, and passive (transient) hyperthyroidism (hyperthyroidism); usually self-limiting); about 5% of patients.
  • With therapy of Graves’ hyperthyroidism, a new occurrence or worsening of endocrine orbitopathy (autoimmune disease with proliferation of connective tissue in the posterior orbit and with a more or less pronounced protrusion of the Aufäpfel) is possible.
  • In patients with autoimmune hyperthyroidism (Graves’ disease), treatment with glucocorticoids accompanying radioiodine therapy seems to reduce the storage of 131J in the thyroid gland.
  • Long-term side effect: hypothyroidism/ hypothyroidism requiring substitution (approximately 20-60% within 5-8 years after therapy); in rare cases, development of immunothyroidism (<5%).
  • Lifelong follow-up due topossible hypothyroidism!
  • There is a theoretical late malignancy risk, particularly affecting organs that come into direct contact with the 131J: Liver (deiodination of thyroid hormones), intestine (131J is excreted via bile), bladder (excretion via kidney), stomach (in case of oral administration), salivary glands (accumulation). A study of 3,637 patients aged less than 25 years who were treated surgically for differentiated thyroid carcinoma (DTC) and then with or without radioiodine therapy resulted in the following: in the group of 1,486 patients who received radioiodine therapy, the standardized incidence ratio (SIR) was: 1.42 (95% confidence interval 1.00 – 1.97; p = 0.037), i.e., a 42% increase in risk.
  • In a cohort study of 18. 805 patients with hyperthyroidism treated with radioactive iodine, a statistically significant positive dose-response relationship for risk of death was observed for all solid cancers (6% increased risk per 100-mGy dose for gastric carcinoma) breast carcinoma/chest cancer (12% increase in risk per 100-mGy dose for breast/stomach cancer) and all solid cancers except breast carcinoma (5% increase in risk per 100-mGy dose for gastric carcinoma).