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Iodine in the treatment of hyperthyroidism

Iodine in the treatment of hyperthyroidism
Author:
Douglas S Ross, MD
Section Editor:
David S Cooper, MD
Deputy Editor:
Jean E Mulder, MD
Literature review current through: Jan 2024.
This topic last updated: Sep 27, 2023.

INTRODUCTION — Iodine solutions, such as saturated solutions of potassium iodide (SSKI) or potassium iodide-iodine (Lugol's solution), replaced burnt sponge extract in the 19th century as treatment for endemic goiter. By extension, they were sometimes used to treat Graves' disease, but by the end of the century, they were considered to be a dangerous form of therapy. They returned to favor in the 1920s as preoperative treatment for hyperthyroidism and were used in the 1930s as the sole therapy for mild hyperthyroidism prior to the introduction of the thionamides. Today, iodine continues to have a minor role in the treatment of hyperthyroidism.

The role of iodine in the treatment of hyperthyroidism will be reviewed here. The treatment of hyperthyroidism in general is reviewed in detail elsewhere. (See "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment" and "Beta blockers in the treatment of hyperthyroidism" and "Thionamides in the treatment of Graves' disease" and "Radioiodine in the treatment of hyperthyroidism".)

MECHANISM OF ACTION — Iodine has several effects on thyroid function. (See "Iodine-induced thyroid dysfunction" and "Thyroid hormone synthesis and physiology".)

In hyperthyroid patients, iodine acutely inhibits hormonal secretion [1], but the responsible mechanisms are uncertain. This is the most acute effect of iodine on thyroid status, occurring within hours of the start of therapy.

A second effect involves inhibition of iodine organification in the thyroid gland, thereby diminishing thyroid hormone biosynthesis, a phenomenon called the Wolff-Chaikoff effect [2]. Patients with Graves' hyperthyroidism are more sensitive to the inhibitory effect of pharmacologic doses of iodine than normal individuals. Thus, iodine is effective in some patients with Graves' disease because it:

Acutely ameliorates hyperthyroidism by blocking thyroid hormone release

Inhibits thyroid hormone synthesis

The overall inhibitory effect of iodine on serum thyroid hormone concentrations is maximal after approximately 10 days of treatment. However, the inhibitory effect may be transient and is often followed by a return to high thyroid hormone concentrations, although the benefit may be more prolonged, especially in patients who have received radioiodine [3].

ROLE OF IODINE — Iodine is primarily used in the short term (frequently for only one to two weeks but sometimes up to four to six weeks) for the following:

Preoperative preparation for thyroidectomy in Graves' disease

Adjunctive therapy (one week after radioiodine or with thionamides) in Graves' disease

Treatment of thyroid storm

We suggest against the routine use of long-term iodine therapy for the treatment of hyperthyroidism. However, long-term iodine may be of benefit in patients with mild disease, including those with thionamide intolerance and a contraindication or aversion to definitive treatment with initial or repeat radioiodine therapy or surgery. (See 'Is there a role for long-term iodine therapy?' below.)

Graves' disease

Preoperative preparation — For preoperative preparation for thyroidectomy in Graves' disease, we suggest short-term iodine (potassium iodide-iodine or potassium iodide solutions) to decrease gland vascularity and surgical blood loss [4-8] and, in patients who are not euthyroid, to lower serum thyroid hormone concentrations.

In a prospective cohort study, the use of preoperative potassium iodide was associated with a lower incidence of transient hypoparathyroidism and hoarseness compared with those who were not given potassium iodine preoperatively [9]. Two small randomized trials showed a significant reduction in blood loss in iodine-treated patients (median estimated blood loss 50 versus 140 mL in the control group), but there were no reported differences in complications (eg, persistent hypocalcemia or permanent recurrent laryngeal nerve injury) [5,7]. Similarly, in a meta-analysis of predominantly observational studies (223 patients given preoperative iodine and 287 controls), the iodine-treated patients had reduced vascularity and reduced intraoperative blood loss, but no change in recurrent laryngeal nerve damage, hypoparathyroidism, or postoperative hematoma [10]. It is typically given for up to 10 days. (See 'Iodine preparations and dosing' below and "Surgical management of hyperthyroidism", section on 'Preoperative preparation'.)

In patients with Graves' disease in regions with iodine deficiency (or hyperthyroid patients with toxic adenoma or toxic nodular goiter), iodine administration may exacerbate hyperthyroidism because the iodine provides more substrate for new hormone synthesis. These patients should not be routinely treated with iodine to reduce gland vascularity preoperatively, and when iodine is used to help lower serum thyroid hormone concentrations, iodine should not be administered until one hour after a thionamide has been given to block thyroid hormone synthesis.

Adjunctive therapy after radioiodine or with thionamides — Potassium iodide may also be beneficial as adjunctive therapy one week after radioiodine (particularly in patients with thionamide intolerance) or with thionamides.

After radioiodine – In selected patients with Graves' disease in whom more rapid normalization of thyroid function is essential but who are allergic to thionamides, saturated solution of potassium iodide (SSKI) given daily, beginning one week after radioiodine, normalizes thyroid function several weeks earlier than in patients given radioiodine alone [11]. (See "Radioiodine in the treatment of hyperthyroidism", section on 'Patients unable to take thionamides'.)

With thionamides – The addition of potassium iodide to thionamides may allow control of hyperthyroidism with a lower dose of thionamide. This may be beneficial in patients experiencing dose-dependent, minor side effects from thionamides. (See "Thionamides in the treatment of Graves' disease", section on 'Dosing'.)

In one randomized trial, low-dose (50 mg) potassium iodide tablets added to methimazole (15 or 30 mg) resulted in normal free thyroxine (T4) levels by two weeks in 54 and 59 percent of patients, respectively, compared with 27 and 29 percent of patients treated with 15 or 30 mg methimazole alone [12].

In a prospective study, 38 mg of iodine added to 15 mg of methimazole resulted in normal free T4 concentrations after 30 and 60 days in 45 and 74 percent, respectively, compared with 25 and 63 percent of patients treated with 30 mg of methimazole without adjunctive iodine [13]. Fewer patients taking 15 mg of methimazole with adjunctive iodine had adverse antithyroid-related side effects compared with those who took 30 mg methimazole without iodine (15 versus 8 percent, respectively).

Is there a role for long-term iodine therapy? — In the absence of more definitive data, we suggest against the routine use of long-term iodine therapy for the treatment of hyperthyroidism. However, long-term iodine may be of benefit in selected patients, including those with thionamide intolerance and a contraindication or aversion to definitive treatment with radioiodine or surgery. The American Thyroid Association (ATA) task force guidelines for management of hyperthyroidism indicate that there is insufficient evidence to assess benefits or risks for the use of long-term iodine treatment [4].

The long-term use of iodine has been reported for the primary medical treatment of patients with Graves' disease (particularly those with thionamide intolerance) or after unsuccessful radioiodine therapy. It has also been used as the primary treatment of pregnant women with Graves' disease. However, the safety of using iodine for hyperthyroid pregnant women is controversial due to concerns that it might cause fetal goiter or hypothyroidism. (See "Hyperthyroidism during pregnancy: Treatment", section on 'Is there a role for iodine as primary therapy for hyperthyroidism?'.)

Primary medical therapy – In Japan, the long-term use of potassium iodide has been reported in patients who had adverse reactions to thionamides. In one study of 44 patients, 66 percent were controlled for an average of 18 years (range 9 to 28 years) and 39 percent achieved remission [14]. In another Japanese study comparing 20 patients with mild hyperthyroidism treated with potassium iodide and 20 treated with methimazole, a similar proportion of patients had normal thyroid function at one year (85 and 95 percent, respectively) [15]. Most patients receiving potassium iodide were treated with 50 mg daily and had mild thyroid dysfunction at baseline.

Primary medical therapy during chemotherapy for cancer – Long-term potassium iodide therapy was also used successfully in five Japanese patients with mild Graves' disease who were receiving potentially neutropenic chemotherapy [16]. Potassium iodide was used rather than methimazole to avoid the possibility of methimazole-induced neutropenia.

Medical therapy after unsuccessful radioiodine treatment – The inhibitory effects of iodine on thyroid hormone release and synthesis are greater in patients previously treated with radioiodine [3]. Thus, potassium iodide can be given months after radioiodine administration to ameliorate mild persistent hyperthyroidism and to delay or prevent the need for a second radioiodine dose.

Primary medical therapy during pregnancy – There are insufficient data to recommend routine iodine for the primary treatment of pregnant women with Graves' disease. Older reports suggested that prolonged, high-dose iodine therapy can cause fetal goiter [17]. However, limited data suggest that low-dose potassium iodide is safe during pregnancy and therefore may have a potential role for the treatment of pregnant women with mild hyperthyroidism who require therapy but are intolerant of thionamides. (See "Hyperthyroidism during pregnancy: Treatment", section on 'Is there a role for iodine as primary therapy for hyperthyroidism?'.)

Because of the known teratogenicity of antithyroid drugs, a preliminary study from Japan compared 1333 hyperthyroid women with Graves' disease who continued antithyroid drugs during pregnancy with 283 who switched to potassium iodine [18]. The incidence of congenital anomalies was lower in the group that switched to iodine (1.5 versus 4.1 percent, respectively), none of the neonates had thyroid dysfunction at birth, and live births were more common in the iodine group (92 versus 85 percent). However, maternal hyperthyroidism was less well controlled.

In another study from Japan, only 1 of 35 neonates exposed to iodine during pregnancy had subclinical hypothyroidism at birth [19].

Thyroid storm — The therapeutic regimen for patients with severe hyperthyroidism or thyroid storm typically consists of multiple medications, each of which has a different mechanism of action. An iodine solution is used to block the release of thyroid hormone. The administration of iodine should be delayed for at least one hour after thionamide administration to prevent the iodine from being used as substrate for new hormone synthesis. (See "Thyroid storm", section on 'Iodine'.)

IODINE PREPARATIONS AND DOSING — The following iodine preparations can be used in the treatment of hyperthyroidism:

Potassium iodide (saturated solution of potassium iodide [SSKI] 50 mg iodide per drop [0.05 mL]) is usually given orally, and diluted in a glass of water or beverage, in a dose of:

0.05 to 0.1 mL (1 to 2 drops, 50 to 100 mg) three times daily for 10 days when used in the preoperative preparation for thyroidectomy in Graves' disease

0.25 mL (5 drops, 250 mg) given four times daily for thyroid storm

0.15 mL (3 drops, 150 mg) given twice daily as adjunctive therapy one week following radioiodine and smaller doses (1 to 2 drops per day) for mild hyperthyroidism that persists months after a dose of radioiodine

Potassium iodide (KI) tablets 130 mg are available in the United States (containing 100 mg iodide).

Potassium iodide-iodine solution (Lugol's, 6.25 mg iodide/iodine per drop) is usually given orally, and diluted in a glass of water or beverage, in a dose of:

0.25 to 0.35 mL (5 to 7 drops) three times daily for 10 days when used in the preoperative preparation for thyroidectomy in Graves' disease

0.5 mL (10 drops) given three times daily for thyroid storm

For patients unable to take oral medication, an alternative is to give the iodine solution per rectum [20].

Dosing errors (administering mL doses when drops were indicated) have been reported with the use of potassium iodide-containing solutions, and therefore, the dose should be carefully reviewed with pharmacy, nursing staff (for treatment of thyroid storm), and the patient [21].

ADVERSE EFFECTS — Iodine administration may exacerbate hyperthyroidism because the iodine provides more substrate for new hormone synthesis. Iodine should generally be administered at least one hour after thionamides or, when used in conjunction with radioiodine, one week later.

Although iodine is typically well tolerated, local esophageal or duodenal mucosal injury and hemorrhage have been reported after oral administration of Lugol's solution (960 mg iodine/day) for the treatment of thyroid storm [22,23]. These solutions can be irritating and should be diluted in 240 mL or more of beverage and taken with food. An acneform facial rash may be dose dependent.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hyperthyroidism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (The Basics)")

Beyond the Basics topics (see "Patient education: Hyperthyroidism (overactive thyroid) (Beyond the Basics)" and "Patient education: Antithyroid drugs (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Mechanism of action – Iodine-containing solutions acutely block the release of thyroxine (T4) and triiodothyronine (T3) from the gland within hours. In addition, administration of pharmacologic amounts of iodine inhibits iodine organification in the thyroid gland. In patients with Graves' disease, the iodine-induced blockade of organification persists and can result in amelioration of hyperthyroidism. The overall inhibitory effect of iodine on serum thyroid hormone concentrations is maximal after approximately 10 days of treatment. (See 'Mechanism of action' above.)

Role of iodine-containing solutions – While largely supplanted by thionamide drugs and radioactive iodine, pharmacologic doses of iodine can still be recommended for the short-term management of hyperthyroid patients in whom rapid restoration of the euthyroid state is beneficial. (See 'Role of iodine' above.)

Preoperative preparation in Graves' disease – For preoperative preparation for thyroidectomy in Graves' disease, we suggest adding potassium iodine solution to decrease the vascularity of the thyroid gland and surgical blood loss (Grade 2B). We typically use saturated solution of potassium iodide (SSKI, 50 mg iodide per drop [0.05 mL], 1 to 2 drops three times daily [approximately 300 mg daily]) for up to 10 days before surgery. (See 'Preoperative preparation' above.)

Thyroid storm – Iodine-containing solutions are routinely used for the treatment of thyroid storm since iodine blocks the release of T4 and T3 from the gland within hours. For patients with thyroid storm or severe thyrotoxicosis, we administer iodine one hour after the first dose of thionamide is taken to prevent the iodine from being used as substrate for new hormone synthesis. (See 'Thyroid storm' above and "Thyroid storm".)

Adjunctive therapy with radioiodine or thionamides – Iodine-containing solutions may also be beneficial as adjunctive therapy one week after radioiodine, particularly in patients with thionamide allergies, or with thionamides. (See 'Adjunctive therapy after radioiodine or with thionamides' above.)

Long-term iodine therapy – We suggest against the routine use of long-term iodine therapy for the treatment of hyperthyroidism (Grade 2C). However, long-term iodine may be of benefit in patients with mild disease, including those with thionamide intolerance and a contraindication or aversion to definitive treatment with radioiodine or surgery. (See 'Is there a role for long-term iodine therapy?' above.)

Available preparations and dosing – Iodine-containing agents include Lugol's solution, potassium iodide (KI) tablets, and SSKI. Dosing varies with the indication. (See 'Iodine preparations and dosing' above.)

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