0021-972X/93/7604-0926$03.00/0 Journal of Clinical Endocrinology and Metabolism Vol. 76, No. 4 Copyright 0 1993 by The Endocrine Society Printed in U.S.A.

Effects of Chronic Iodine Administration on Thyroid Status in Euthyroid Subjects Previously Treated with Antithyroid Drugs for Graves’ Hyperthyroidism*

ELI0 ROTI, ELIANA GARDINI?, ROBERTA MINELLI?, LINA BIANCONI, MARIO SALVI, GILBERT0 GAVARUZZI, AND LEWIS E. BRAVERMAN Centro per lo Studio, Preuenzione, Diagnosi e Cura della Tireopatie, Cattedra di Endocrinologia, Uniuersitci di Parma, and Servizio di Medicina Nucleare, Ospedali Riuniti di Parma, Parma, Italy; and the Division of Endocrinology and Metabolism, University of Massachusetts Medical School, Worcester, Massachusetts 01655

ABSTRACT and T, concentrations; thyroid hormone values and TRH tests were In view of the adverse effects of the administration of pharmacolog- normal in the other 8 patients and similar to values observed in 4 ical quantities of iodine to euthyroid patients with a history of a wide euthyroid women without a history of thyroid disease given SSKI. variety of thyroid disorders, it has been suggested that iodine-contain- Serum AbTPO increased slightly, but significantly, during SSKI ad- ing medications and radioopaque dyes containing iodine should be ministration in the 7 women with positive values at baseline (P < 0.05). avoided, if possible, in patients with underlying thyroid disease. We TSH-RAb remained undetectable. After SSKI withdrawal, the 10 have now prospectively studied the effects of pharmacological doses of women were reevaluated 60 and 120 days later. Two women developed a saturated solution of potassium iodide (SSKI) on thyroid function in a blunted TSH response to TRH, but normal serum Ta and T, concen- euthyroid patients with a previous history of hyperthyroid Graves’ trations, and 2 women developed overt hyperthyroidism, with unde- disease successfully treated with antithyroid drugs. Ten euthyroid tectable basal and TRH-stimulated serum TSH and elevated serum Tq women (mean age, 56 yr) who had hyperthyroid Graves’ disease suc- and TS concentrations, requiring methimazole therapy. All values in cessfully treated with methimazole 36.4 + 4.7 months earlier were the remaining 6 women were similar to those present before SSKI evaluated before, during, and after the administration of 10 drops SSKI administration. These results suggest that some euthyroid patients daily for 90 days. The following thyroid function tests were obtained: with a history of antithyroid drug therapy for Graves’ disease may serum T1, Ts, TSH, TSH receptor antibody (TSH-RAb), and anti- develop thyroid dysfunction during and after excess iodine administra- thyroid peroxidase antibody (AbTPO) concentrations; TRH tests; and tion. The development of subclinical hypothyroidism during SSKI iodine perchlorate discharge tests. Serum T,, Ts, basal and TRH- administration was not clinically important, but the occurrence of overt stimulated TSH, and TSH-RAb values were normal before SSKI hyperthyroidism after SSKI was discontinued did require antithyroid administration, but serum AbTPO levels were markedly positive in 7 drug therapy. It is advisable, therefore, to avoid iodine-containing and iodine perchlorate discharge tests were positive in 4 of these 10 substances in euthyroid patients with a history of antithyroid drug women. During SSKI administration, basal and TRH-stimulated serum therapy for Graves’ disease. (J Clin Endocrinol Metub 76: 928-932, TSH values increased above normal in 2 women with normal serum T, 1993)

ODINE- induced hyperthyroidism has been observed in In euthyroid patients previously treated with 1311and I patients with euthyroid nodular goiter, patients with sub- partial thyroidectomy for Graves’ disease,iodine administra- clinical Graves’ disease,and subjects without any apparent tion may induce hypothyroidism (6). Studies on the effects thyroid disease(1, 2). In the patients with subclinical Graves’ of iodine administration in euthyroid subjects previously disease,iodine administration and an increase in dietary treated with antithyroid drugs for Graves’ hyperthyroidism iodine intake have been reported to induce and exacerbate have yielded conflicting results (7, 8). In the present study, the hyperthyroidism (l-3). Furthermore, it has been sug- we have evaluated the effects of pharmacological amounts gested that increased dietary iodine intake is associatedwith of iodine on thyroid function in euthyroid subjectspreviously an increased recurrence rate of hyperthyroidism in patients treated with methimazole (MMI) for hyperthyroid Graves’ previously treated with antithyroid drugs for Graves’ disease disease. (4, 5).

Received July 6, 1992. Materials and Methods Address requests for reprints to: Dr. Elio Roti, Cattedra di Endocri- nologia, Universiti di Parma, via Gramsci 14, 43100 I’arma, Italy. Ten women (mean age, 56 + 2.5 yr) who had Graves’ disease treated *This work was supported in part by Grants 89.04244.04, with MM1 for 19.3 -+ 2.9 months (range, 8-38 months) were enrolled in 0.01540.CT04, and 91.00316.CT04 from Consiglio Nazionale delle Ri- the present study after informed consent was obtained. The mean daily cerche (Rome, Italy); Grant ‘Patologia della Tiroide: Indagine dei Fattori dose of MM1 was 9 mg. These subjects had been euthyroid for 36.4 + Etiopathogenetici” of Minister0 Pubblica Istruzione 40% (Rome, Italy); 4.7 months after MM1 was discontinued before entering the present Grant Ricerca Finalizzata Regione Emilia-Romagna 1988-1990; and study. Grant DK-18919, NIH (Bethesda, MD). Before iodide administration, thyroid status was evaluated clinically t Recipient of a fellowship from Associazione Volontaria Promozione and by thyroid function tests (serum T,, T3, and basal and TRH- Ricerca Tumori (A.VO.PRO.RI.T.), Parma, Italy. stimulated TSH concentrations). The 10 women were euthyroid (EG).

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Five patients had grade Ia goiter, and 5 had grade II goiter according to Results WHO criteria. Circulating antithyroid peroxidase antibodies (AbTPO) and TSHreceptor antibodies (TSH-RAb) were measured. The TSH assay Thyroid status before SSKZ administration (baseline) is an immunoradiometric assay employing a monoclonal antibody la- beled with 125I which binds to a unique site on the TSH molecule. A Serum Til, T3, and basal and TRH-stimulated TSH concen- second monoclonal antibody linked to fluorescein binds on the TSH trations in the EG subjectswere similar to those observed in molecule, forming a sandwich. After incubation, antifluorescein coupled control subjects (Table 1). Furthermore, none of the EG to a magnetic solid phase is added in excess. This binds to the TSH- subjectshad elevated or suppressedserum TSH responsesto monoclonal antibody complex and is sedimented in a magnetic field. TRH. An iodide perchlorate (I-Clod) discharge test was carried out in the 10 EG subjects. A tracer dose of i3’I (5 PCi) was administered orally I-ClO, discharge tests were positive in 4 of the 10 EG with 500 pg stable I at zero time. Three hours later, thyroid i3’I uptake subjects and in none of the 8 control subjects (P < 0.01, by was measured, followed by the oral administration of 1 g potassium Fisher’s exact test). perchlorate (KCIO,). The thyroid i3’I uptake test was repeated 1 h after Serum AbTPO levels were elevated in seven EG subjects, KCIO( administration. An abnormal test was defined as a discharge of four of whom had positive I-ClO, discharge tests. The mean i3iI greater than 15% 1 h after KC104 administration. A TRH test was AbTPO level was 3954 f 2222 U/ml. Serum TSH-RAb were carried out to evaluate pituitary TSH reserve. Serum samples for TSH measurement were obtained before and 20 min after the iv administra- not detected in any of the Eg subjects. AbTPO and TSH- tion of 200 pg TRH (Ares-Serono, Milan, Italy). RAb were undetectable in the control subjects. After these studies were completed, 10 drops of a saturated solution Urinary iodine excretion in the 14 women averaged 162 of potassium iodide (SSKI; 350 mg iodide) were given daily, and serum PLgiodine/g creatinine. was obtained for thyroid function tests on days 15, 30, 60, and 90 of treatment and 60 and 120 days after SSKI was discontinued. The TRH test was repeated on the last day (day 90) of SSKI administration and Thyroid status during SSKZ administration 60 and 120 days later. Serum samples were kept frozen at -20 C until the study was During SSKI administration, there was no significant completed. All samples were assayed in the same assay, in duplicate, change in serum TSH concentrations in the control subjects; and in random order. Serum T4 and T3 concentrations were measured the highest value was observed on day 60 (mean f SD, 3.5 by RIA, and serum TSH by a sensitive immunoradiometric method with + 2.5 mu/L). On day 90 of SSKI administration, the control materials obtained from Ares-Serono. Normal ranges for serum thyroid women had a mean serum TSH response to TRH of 21.8 f hormone concentrations are as follows: Tl, 57.9-154.5 nmol/L; TS, 0.92- 3.07 nmol/L; TSH, 0.2-6.5 mU/L. The intraassay coefficients of variation 10.9 mU/L (mean + SD), a value significantly higher than were 1.4% for T4, 3.4% for T3, and 4.2% for TSH. AbTPO and TSH- that observed before SSKI administration (P < 0.01, by RAb were measured by RIA and a radioreceptor binding assay, respec- Student’s t test). Basedon the values observed in the normal tively, with materials obtained from Henning-Berlin GmBH (Berlin, women, basal and TRH-stimulated serum TSH values higher Germany). Levels of serum AbTPO and TSH-RAb higher than 100 U/ than 8.5 and 43.6 mu/L, respectively, were consideredto be mL and 15 U/L, respectively, were considered to be positive. Urinary iodine excretion was measured in a morning urine sample by the method elevated. Serum T4 and T3 concentrations did not change in of Benotti et al. (9), and values of iodine excretion were calculated as the control subjects during SSKI administration. micrograms per g creatinine. During SSKI administration, one EC subject had serum I-ClO, discharge tests were carried out in 8 euthyroid women, aged TSH concentrations of 10.6 and 15.9 mU/L on days 30 and 30.5 + 2.2 yr, who had never had autoimmune thyroid disease (10). All 60, respectively, and another had a TSH response to TRH had a negative I-Cl04 discharge test. TRH tests were carried out in 4 of on day 90 of 50.1 mU/L (Table 2). Thus, these 2 EG patients these women who were then given SSKI and studied over the same period of time as the 10 EG subjects. with elevated basal or TRH-stimulated serum TSH concen- Basal serum TSH concentrations in the EG subjects before SSKI trations were considered to have iodine-induced subclinical administration were considered elevated when they exceeded the mean hypothyroidism, since serum T4 and T3 concentrations during + 2 SD of values in the control subjects. During SSKI administration, the SSKI administration fluctuated within the normal range, and EG patients were considered to have elevated serum TSH concentrations signs of hypothyroidism were not observed (Table 2). Both when one or more serum TSH values were higher than the highest mean patients had elevated serum AbTPO concentrations before + 2 SD of TSH concentrations in the control subjects during SSKI and during SSKI administration, and one had a positive I- administration. TRH-stimulated serum TSH concentrations in EG sub- jects were considered elevated when they were higher than the corre- sponding mean + 2 SD of values in control subjects (11). EG subjects TABLE 1. Serum Tq, Ts, and basal and TRH-stimulated serum were considered to have iodine-induced subclinical hypothyroidism TSH concentrations in EG subjects previously treated for Graves’ when basal and/or TRH-stimulated serum TSH concentrations during hyperthyroidism with MM1 and in control subjects before SSKI administration SSKI administration were elevated. Basal and TRH-stimulated serum TSH concentrations were considered suppressed when they were lower EG (n = 10) Controls (n = 4) than 0.2 mu/L. Statistical analysis was carried out by paired and unpaired Student’s T, (nmol/L) 111.3 f 6.4 96.5 + 15.8 t tests to compare thyroid function tests before and after SSKI adminis- T, (nmol/L) 1.9 + 0.1 1.8 f 0.2 tration and the TSH response to TRH at baseline, on day 60 of SSKI Basal TSH (mu/L) 1.2 + 0.2 1.5 zk 0.5 administration, and 60 and 120 days after SSKI was withdrawn, in the 20 min TSH responses to 10.7 + 2.4 13.5 + 3.9 same group and between the groups; one-way analysis of variance (1 TRH (mu/L) way ANOVA) was used to evaluate hormone patterns in EC and control The number of subjects in each group is in parentheses. Values are subjects during SSKI administration, and Fisher’s exact test was em- the mean f SE. No significant difference was observed in thyroid ployed to evaluate the prevalence of abnormal tests in different groups. function tests between EG and control subiects. None of the EG All values are reported as the mean + SE, except when otherwise subjects had elevated or suppressed basal and TRH-stimulated serum indicated. TSH concentrations.

Downloaded from jcem.endojournals.org at Eidgenossische Technische Hochschule Bibliothek on September 8, 2008 ROT1 ET AL. JCE & M .1993 Vol76.No4 TABLE 2. Serum TI, Ts, and basal and TRH-stimulated serum TABLE 3. Serum T1, TS, and basal and TRH-stimulated serum TSH concentrations in the two patients who developed iodine- TSH concentrations in the two patients who developed induced subclinical hypothyroidism during SSKI administration hyperthyroidism after SSKI withdrawal

Days after Days on SSKI Days after SSKI Days on SSKI SSKI Patient no. Patient no. 0 15 30 60 90 60 120 0 15 30 60 90 60 120 T, (nmol/L) Tq (nmol/L) 1 118 104 87 87 104 95 3 118 112 115 122 117 230 2 109 78 94 93 104 112 89 4 138 113 104 112 115 138 234 T1 (nmol/L) T, (nmol/L) 1 1.5 1.8 1.4 1.4 1.7 1.4 3 2.0 1.9 2.0 2.1 2.3 3.9 BLaI TSH (mu/L) 1.8 1.5 1.7 1.7 1.9 1.6 1.6 4 2.0 1.5 2.0 2.1 2.2 2.5 4.3 Basal TSH (mu/L) 1 2.9 2.4 10.6 15.9 5.3 0.7 3 0.7 2.1 1.6 1.7 0.6 0.1 2 1.6 3.1 1.7 3.3 4.7 1.8 0.1 4 0.8 3.1 3.6 3.3 5.9 0.9 0.1 20 min TSH response 20 min TSH response to TRH (mu/L) to TSH (mu/L) 1 29.8 35.1 9.2 3 7.1 4.6 0.1 2 15.2 50.1 21.3 3.2 4 9.7 41.4 9.9 0.1 Patient 1 became clinically hyperthyroid 60 days after SSKI was C104discharge test. discontinued, and patient 2 developed clinical hyperthyroidism 120 days after SSKI was discontinued. Both patients were treated with The other eight EG subjects had a slight increase in basal MMI. serum TSH concentrations during SSKI administration, reaching the highest value on day 60 (3.9 + 1.4 mu/L; P < with a blunted TSH response to TRH had serum T4 and T3 0.01, by 1 way ANOVA). In these eight EG subjects, the concentrations within the normal range. These two subjects TSH response to TRH on day 90 was 21.9 f 4.3 mu/L, did not have any signsor symptoms of hyperthyroidism. significantly higher than that observed before SSKI admin- One hundred and twenty days after SSKI was discontin- istration (P < 0.01, by Student’s t test), but not different from ued, a second EG patient had an undetectable serum TSH values in the control subjectson day 90. During SSKI admin- concentration and no TSH responseto TRH and had elevated istration, no EG patient had suppressed basal and TRH- serum T4 and TX concentrations of 234.3 and 4.3 nmol/L, stimulated TSH concentrations. respectively (Table 3). This patient was clinically hyperthy- In the eight euthyroid EG subjects, serum T4 concentra- roid and was also treated with MMI. The two EC subjects tions did not change during SSKI administration, whereas who had a blunted TSH responseto TRH continued to have serum T3 concentrations showed a significant increase, reach- a reduced TSH response,had serum T4 and TJ concentrations ing the highest value on day 90 (2.1 + 0.1 nmol/L; P < 0.05, within the normal range, and had no signs or symptoms of by 1 way ANOVA). However, none of these subjects had hyperthyroidism. Thus, by 120 days after SSKI was discon- serum T3 concentrations above the upper limit of normal. tinued, two patients had developed hyperthyroidism, two In the seven AbTPO-positive EG subjects, the antibody patients had a blunted TSH response to TRH but remained levels slightly, but significantly, increased (P < 0.05, by l- euthyroid, and six patients remained euthyroid with normal way ANOVA) during SSKI administration, reaching a peak basal and TRH-stimulated serum TSH values. of 5478 f 2437 U/ml on day 90. Serum TSH-RAb remained The 24-h thyroid lz31 uptakes in the two hyperthyroid undetectable during SSKI administration. Serum AbTPO and patients during MM1 treatment were 37% and 49%, respec- TSH-RAb remained undetectable in the control women. tively. Thyroid function tests in the six EG patients who did not Thyroid status after SSKZ develop thyroid dysfunction and in the four control women SSKI was discontinued after day 90, and all subjects were before, during, and after SSKI administration are reported in Table 4. reevaluated 60 and 120 days later. Serum TSH was unde- tectable on day 60 and did not increase after TRH in one EG After SSKI was discontinued, serum TSH-RAb remained undetectable in all control and EG subjects, including the patient (Table 3). The TSH response to TRH was blunted in two EG patients who developed hyperthyroidism. two others. The two EG women who had elevated basal or TRH-stimulated serum TSH concentrations during SSKI ad- ministration had serum basal and TRH-stimulated TSH val- Discussion ues similar to those observed before SSKI was administered. The remaining five EG subjects had basal and TRH-stimu- In previous studies, it has been suggested that iodine- lated serum TSH concentrations similar to those observed induced hyperthyroidism may occur in subjectswith subclin- before SSKI administration. The EG subject with undetecta- ical Graves’ disease (1). Subjects residing in an endemic ble serum TSH and no TSH response to TRH had serum T4 iodine-deficient goiter area with positive circulating long- and T3 concentrations above the upper limit of normal (230 acting thyroid stimulator or long-acting thyroid stimulator and 3.95 nmol/L, respectively; Table 3), was clinically hy- protector developed hyperthyroidism during iodine prophy- perthyroid, and was treated with MMI. The two EG patients laxis, suggesting that Graves’ hyperthyroidism was not pre-

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TABLE 4. SerumT,, TB,and basal and TRH-stimulatedserum TSH concentrationsbefore, during, and after SSKI administrationin six EG subjectswho remained euthyroid during and after SSKI administrationand in the four control women(C)

Days on SSKI Days after SSKI 0 15 30 60 90 60 120 T, (nmol/L) EG 105f 9 102 + 8 98 + 5 98 + 6 98 + 9 124 + 11 101 + 10 C 96 + 16 93 + 7 96f 12 96 + 9 99 + 5 88 If: 6 TB(nmol/L) EG 1.9 + 0.1 1.8 + 0.1 1.8 + 0.1 1.9 + 0.1 2.0 + 0.1 2.1 + 0.1 2.0 + 0.1 C 1.8 + 0.2 2.1 + 0.2 1.9 + 0.2 1.8 + 0.2 1.8 + 0.1 1.8 + 0.2 TSH (mu/L) EG 0.9 f 0.2 2.7 + 0.6 2.0 Tk 0.4 2.5 + 0.8 3.0 f 0.9 0.7 I? 0.2 0.8 + 0.2 C 1.5 + 0.5 3.3 + 1.3 2.8 + 0.6 3.5 + 1.5 3.2 + 1.1 1.3 + 0.4 20 min TSH responseto TRH (mu/L) EG 7.5 + 1.1 21.5 + 3.5 6.6 f 3.3 6.4 + 1.7 C 13.5 * 3.9 21.8 + 6.3 8.4 + 1.9 All valuesare the meanf SE. viously present due to inadequate iodine intake (12). Patients after iodine was discontinued (18). In a single patient with with T3 toxicosis due to latent Graves’ disease may also iodine-induced hyperthyroidism, further iodine administra- develop overt hyperthyroidism after iodine administration tion resulted in an amelioration of the hyperthyroidism (19). (13). Furthermore, it has been suggestedthat increased die- These findings suggest that the effects of iodine on thyroid tary iodine intake was associated with an increased recur- function in patients with active or potential hyperthyroidism rence rate of Graves’ hyperthyroidism (4,5). In a prospective are probably due to at least two mechanisms. First, excess study, the administration of small quantities of iodine (200 iodine partially decreasesthyroid hormone release from the &day) to euthyroid subjectsimmediately or 6 months after gland, especially in patients with hyperthyroidism (20), thus antithyroid drugs were discontinued in patients with Graves’ partially explaining the transient improvement during iodine diseaseinduced a small increase in the serum protein-bound therapy in hyperthyroid patients. Second, iodine administra- iodine concentration and an increased recurrence rate of tion may result in continued and even excessivesynthesis of clinical hyperthyroidism (7). However, in another study, thyroid hormones, especially in areas of decreased iodine Thalassinosand Fraser (8) reported that the administration intake or in thyroids with diffuse or nodular autonomy. of 10 mg iodine daily to euthyroid subjectspreviously treated In the two EG patients who developed hyperthyroidism with antithyroid drugs for Graves’ diseasedid not increase after SSKI was discontinued, serum TSH-RAb were not the recurrence rate of hyperthyroidism. Patients thyroidec- present before, during, and after iodine administration. This tomized for Graves’ diseasewho resided in an area with an finding does not exclude the diagnosis of recurrent Graves’ elevated iodine intake had a higher recurrence rate of hyper- disease,since it has been reported that not all patients with thyroidism than patients residing in an area with a low iodine Graves’ diseasehave TSH-RAb (21). It is unlikely that these intake (14). Finally, antithyroid drugs were less effective in two EG patients had autonomous thyroid function before controlling the hyperthyroidism of patients residing in a and during SSKI administration, since basal and TRH-stim- region with adequate iodine intake than in patients living in ulated serum TSH concentrations were normal. Others have an area of low iodine intake (15). observed focal inflammatory lesions in the thyroids from In the present study, we observed that euthyroid subjects patients with iodine-induced hyperthyroidism, suggestinga with a previous episode of Graves’ hyperthyroidism treated destructive process with leakage of thyroid hormones into with MM1 did not develop hyperthyroidism during the ad- the blood (22). We did not observe any signs or symptoms ministration of large amounts of iodine. However, two pa- suggesting subacute thyroiditis in the two EG patients who tients developed hyperthyroidism after SSKI was discontin- developed hyperthyroidism after iodine withdrawal. Thus, ued. Vagenakis et al. (16) observed that subjects with non- in the two EG subjectswho developed hyperthyroidism after toxic nodular goiter treated with pharmacological amounts iodine was discontinued, the onset of hyperthyroidism may of SSKI developed mild hyperthyroidism, which became far have been due to increased synthesis of thyroid hormone worse after iodine was discontinued. Emerson et al. (17) and partial inhibition of hormone release during iodine ad- observed that iodine administration to patients with hyper- ministration, with a subsequent release of stored hormone thyroid Graves’ diseasedecreased serum thyroid hormone after iodine withdrawal. It is also possible that these two concentrations, although a rebound increase was observed patients might have developed spontaneous recurrent hy- during the continued administration of iodine. We have perthyroidism regardlessof iodine administration. previously observed that patients with hyperthyroid Graves’ A positive I-ClO, dischargetest is a marker of an intrathy- diseasehad normal serum thyroid hormone concentrations roid iodine organification defect and subsequent decreased during iodine administration, but that serum thyroid hor- hormone synthesis (23, 24), but may also be due to an mone concentrations rapidly rebounded to elevated values increasedintrathyroid iodide content due to enhanced trap-

Downloaded from jcem.endojournals.org at Eidgenossische Technische Hochschule Bibliothek on September 8, 2008 932 ROT1 ET AL. JCE&M.1963 Vo116.No4 ping of iodide, since a large number of patients newly 9. Benotti J, Benotti M, Pino S, Gardvna H. 1965 Total iodine in diagnosed with Graves’ hyperthyroidism have a positive urine, stool, diets, and tissue. Clin Chem. 11:932-936. 10. Roti E, Minelli R, Gardini E, et al. 1991 Imuaired intrathvroid iodine discharge test (our personal observation). In the pres- iodine brganificatidn, iodine-inhuced hypothyrdidism in euthyroid ent study, only 4 of 10 euthyroid women previously treated women with a previous episode of postpartum thyroiditis. J Clin with MM1 for hyperthyroid Graves’ diseasehad a positive I- Endocrinol Metab. 73:958-963. C104 discharge test, and only 1 developed iodine-induced 11. Stromme JH, Eliarn L. 1970 Surveys of the routine work of clinical chemical laboratories in 116 Scandinavian hospitals. Stand J Clin subclinical hypothyroidism. The other patient who devel- Lab Invest. 25:213-222. oped iodine-induced subclinical hypothyroidism had a neg- 12. Adams DD, Kennedy TH, Stewart JC, Utiger RD, Vider SI. 1975 ative I-Clod discharge test. This is in contrast to the high Hyperthyroidism in Tasmania following iodide supplementation: prevalence of iodine-induced hypothyroidism and positive measurements of thyroid-stimulating autoantibodies and thyrotro- pin. J Clin Endocrinol Metab. 41:221-228. I-ClO, discharge tests in euthyroid patients previously 13 Rajatanavin R, Safran M, Stoller WA, Mordes JP, Braverman LE. treated for active Graves’ disease with definitive therapy, 1984 Five patients with iodine-induced hyperthyroidism. Am J Med. such as radioactive iodine and subtotal thyroidectomy (6); in 77:378-384. euthyroid patients with a history of inflammatory thyroid 14. 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