Graves' hyperthyroidism treated with potassium iodide: early response and after 2 years of follow-up

Abstract

Objective: As thionamide is associated with various adverse effects, we re-evaluated the practical efficacy of potassium iodide (KI) therapy for Graves' hyperthyroidism (GD).

Methods: We administered KI (mainly 100 mg/day) to 324 untreated GD patients and added methimazole (MMI) only to those remaining thyrotoxic even at 200 mg/day. When the patient became hypothyroid, MMI, if taken was stopped, then levothyroxine (LT4) was added without reducing the KI dose. Radioactive iodine (RI) therapy or thyroidectomy was performed whenever required. We evaluated the early effects of KI at 2-4 weeks and followed patients for 2 years.

Results: At 2 weeks, serum thyroid hormone levels decreased in all 324 patients. At 4 weeks, fT4, fT3, and both fT4 and fT3 levels became normal or low in 74.7%, 50.6%, and 50.6% of patients, respectively. In a cross-sectional survey over 2 years, GD was well-controlled with KI or KI + LT4 (KI-effective) in >50% of patients at all time points. Among 288 patients followed for 2 years, 42.7% remained 'KI-effective' throughout the 2 years (KI Group), 30.9% were well-controlled with additional MMI given for 1-24 months, and 26.4% were successfully treated with ablative therapy (mainly RI). Among 'KI-effective' patients at 4 weeks, 76.5% were classified into the KI Group. No patients experienced adverse effects from KI.

Conclusion: KI therapy was useful in the treatment of GD. A sufficient dose of KI was effective in >50% of GD patients from 4 weeks to 2 years, and 42.7% (76.5% of 'KI-effective' patients at 4 weeks) remained 'KI-effective' throughout the 2 years.

Keywords: Graves’ disease; hyperthyroidism; iodine; potassium iodide.

Figure 1

Flowchart showing the inclusion process for participants. GD, Graves’ hyperthyroidism; KI, potassium iodide; MMI, methimazole; RI, radioactive iodine therapy; PTU, propylthiouracil. *Subjects of the early response study, **Subjects of the cross-sectional follow-up study, ***Subjects of the treatment groupings and the comparative study.

Figure 2

Simplified treatment schema for Graves’ hyperthyroidism in this study. Participants were constantly moving between different treatment groups depending on their conditions. KI, potassium iodide (mg/day); LT4, levothyroxine (μg/day); MMI, methimazole (mg/day); Hyper, hyperthyroid; Eu, euthyroid; Hypo, hypothyroid. The ranges of doses for each drug used were as follows: KI, from 50 mg every other day to 200 mg/day; LT4, from 25 to 100 μg/day; MMI, from 5 mg every other day to 30 mg/day.

Figure 3

Changes in serum levels of fT4 (A) and fT3 (B) at 2 and 4 weeks after starting potassium iodide (KI) treatment in 324 patients with untreated Graves’ hyperthyroidism. 2W, 2 weeks; 4W, 4 weeks after starting KI. [1] High sensitivity to KI: fT4 <1.8 ng/dL or fT3 <4.4 pg/mL at both 2 and 4 weeks. [2] Clinical escape from the KI effect: fT4 <1.8 ng/dL or fT3 <4.4 pg/mL at 2 weeks, but fT4 >1.8 ng/dL or fT3 >4.4 pg/mL at 4 weeks. [3] Sensitive but required a higher dose of KI: fT4 >1.8 ng/dL or fT3 >4.4 pg/mL at 2 weeks, but fT4 <1.8 ng/dL or fT3 <4.4 pg/mL at 4 weeks after doubling the dose of KI. [4] Resistance to KI: fT4 >1.8 ng/dL or fT3 >4.4 pg/mL at both 2 and 4 weeks. *Only one patient showed a higher fT3 level at 4 weeks than before treatment.

Figure 4

How the patients with Graves’ hyperthyroidism were treated to maintain euthyroid status at each point (A: 6 weeks, B: 3 months, C: 6 months, D: 1 year, and E: 2 years): Cross-sectional survey. [1] P/R (possible remission): showing non-suppressed TSH and negative TRAb without medications [violet area]. [2] KI + LT4: taking potassium iodide (KI) and levothyroxine (LT4) (navy area). [3] KI only: taking KI alone (blue area). [4] KI + MMI < 15: taking KI and methimazole (MMI) <15 mg/day (yellow area)]. [5] KI + MMI ≥ 15: taking KI and MMI ≥15 mg/day (orange area). [6] RI: within 3 months after ¹³¹I treatment (RI) (black area). [7] KI + MMI after RI: taking KI and MMI >3 months after RI (pink area). [8] KI after RI: taking KI or KI + LT4 >3 months after RI (green area). [9] Hypo after RI: taking LT4 alone (hypothyroid) after RI (brown area). [10] Op: taking LT4 alone (hypothyroid) after total thyroidectomy (red area). The numbers of patients who dropped out in each interval were as follows: (between A and B) KI only, n = 1; KI + MMI < 15, n = 2, (between B and C) KI only, n = 3, KI + MMI < 15, n = 3; KI + MMI ≥ 15, n = 1, (between C and D) KI + LT4, n = 2; KI only, n = 3; KI + MMI < 15, n = 3; KI after RI, n = 2, (between D and E) P/R, n = 1; KI+LT4, n = 1; KI only, n = 6; KI + MMI < 15, n = 4; KI after RI, n = 2; Hypo after RI, n = 2. (F) Summarized classification of 288 patients followed for 2 years. KI Group: patients who were well-controlled with KI alone or KI + LT4 throughout 2 years. KI + MMI Group: patients who required combination therapy of KI + MMI even for a short period, without ablative therapy, to maintain euthyroid status. Ablation Group: patients who were treated with ¹³¹I therapy (RI) or total thyroidectomy (Op) during 2 years.

Figure 5

Data on combination therapy with potassium iodide (KI) and methimazole (MMI) or radioactive iodine (RI) therapy in patients with Graves’ hyperthyroidism. (A) Duration (months) for which MMI was required during KI treatment in the KI + MMI Group. Thirty (33.7%) patients continuously required MMI for 2 years. In 23 (25.8%) patients, MMI was used for a short period of less than 1 year. (B) Maximum daily dose of MMI required during KI treatment in the KI + MMI Group. The maximum daily dose of MMI was 12.2 ± 4.4 mg on average, and it was only 5–10 mg/day in 47 of 89 (52.8%) patients. In the KI + MMI Group, only one patient took MMI up to 30 mg/day, and most of the patients who required high doses of MMI (>15 mg/day) promptly chose ablative therapy before they actually took such high doses of MMI. One patient who had required MMI 30 mg/day could reduce the dose to 15 mg/day. In six patients who had taken MMI 20 mg/day, two could reduce the dose to 10 mg/day, three to 5 mg every other day, and one could stop MMI, resulting in ‘KI effective’ state. (C) ¹²³I uptake just before RI therapy in KI-treated patients after restriction of iodide for 5–7 days. Most of the patients could achieve sufficiently high thyroid ¹²³I uptake (median 65.0%/5 h). In our district, the urinary iodide excretion was 585 (274–1362) µg/gCr in euthyroid controls (n = 93), and 228 (124–723) µg/gCr in untreated Graves’ hyperthyroidism (n = 100) (unpublished data).