Relapses of hyperthyroidism in patients treated with radioiodine for nodular toxic goiter: Relation to thyroid autoimmunity

Abstract

Relapses of hyperthyroidism after treatment with radioiodine for uni- or multi-nodular goiter may be accompanied by the appearance of TSAb. However, this phenomenon has only emerged from one retrospective study on Northern European patients, in which it was not possible to determine whether TSAb also appeared in treated patients who did not relapse. The present study aimed to assess the appearance, immunogenic nature and clinical characteristics of hyperthyroidism relapse after treatment with 131I for nodular toxic goiter in patients from the Mediterranean area. A retrospective study was performed on 76 consecutive patients, born and resident in Sicily and aged 56-80 yr at diagnosis, who were treated with radioiodine. Serum aliquots obtained from the patients before 131I treatment and during a follow-up of 36-144 months were assayed for TSAb and TPOAb. The clinical charts of the patients were also re-examined. Twenty-six out of 76 patients (36.8%) had a hyperthyroidism relapse after a first treatment with 131I. Eight of the 26 (30.7%) also relapsed after the second treatment. Three out of 26 (11.5%) relapsed after a third treatment. The 50 patients who required only one treatment and the 18 who relapsed only once were all TSAb-negative at baseline, while 3/8 (37.5%) who relapsed also after the second treatment were already TSAb-positive at baseline. TSAb became positive in 3/18 patients (16.7%) who relapsed once, and in 4/8 (50.0%) of those who relapsed after a second treatment. One of these 7 TSAb-positive relapsers was also already TPOAb-positive at baseline and another became TPOAb-positive after treatment. The presence of circulating TSAb in 3/76 (3.9%) patients before treatment for toxic goiter more probably points to a diagnosis of Marine-Lenhart's syndrome. In contrast, the de novo appearance of TSAb in the presence of hyperthyroidism relapse in 4/76 (5.3%) patients suggests the development of a Graves'-like disease after radioiodine treatment. This occurrence does not seem to have precise ethnic grounds, since the incidence we observed in Mediterranean patients was similar to that previously reported in Northern European patients.

The Marine-Lenhart syndrome revisited

“…Th is phenomenon was observed already in 1993: Boddenberg et al [2] were the fi rst to publish results in eight patients who had developed Graves' disease after RIT of autonomous thyroid disease. Similar data were published by Italian researchers [3]: Th e presence of circulating TSH receptor antibodies before treatment for toxic goiter was observed in 3.9% (3/76). Some other papers from Germany [4] and Turkey [5] focused on this problem.…”

An uncommon case of Marine-Lenhart syndrome

“…There is literature on the risk that Graves-like hyperthyroidism may develop after radioiodine treatment in patients with elevated serum TPO-Ab levels at baseline (15,16), as well as in TPOAb-negative patients at baseline who became TPOAb-positive after treatment (17,18). Therefore, it could be hypothesized that, in a subject genetically susceptible to thyroid autoimmunity, follicular cell damage caused by radioiodine could trigger an autoimmune response against TSH receptors, thus explaining the occurrence of Graves' disease after radioiodine therapy (15)(16)(17)(18). Unlike most cases reported in the literature, our particular case of Marine-Lenhart syndrome shows the appearance of an AFTN as a consequence of Graves' disease treatment with radioiodine.…”

“…Since the first description in 1911 by Marine and Lenhart (3), the presence of focal autonomy in patients with Graves' disease has been reported by numerous authors, and with different presentations (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), with an overall prevalence of such association ranging from 2.7% to 4.1% (4). Moreover, during the last years, several papers have been published on the development of Graves' disease shortly after radioiodine therapy for AFTNs (15)(16)(17)(18). The incidence of this event is significantly higher, especially in patients with elevated serum thyroid peroxidase antibodies (TPO-Ab) levels at baseline (15,16), as well as in patients TPOAb-negative at baseline who became TPOAb-positive after treatment (17,18).…”

“…Moreover, during the last years, several papers have been published on the development of Graves' disease shortly after radioiodine therapy for AFTNs (15)(16)(17)(18). The incidence of this event is significantly higher, especially in patients with elevated serum thyroid peroxidase antibodies (TPO-Ab) levels at baseline (15,16), as well as in patients TPOAb-negative at baseline who became TPOAb-positive after treatment (17,18).…”

“…Thus, our patient developed an AFTN three years after the onset of hyperthyroidism due to Graves' disease that was successfully treated with radioiodine. Looking at the pertinent literature (15)(16)(17)(18), we present our case as a variant of classic Marine--Lenhart syndrome. When the "hot" nodule was discovered, there was no diffuse increase in radiotracer uptake by the gland and TRAb were negative, because hyperthyroidism due to Graves' disease -diagnosed three years before -was successfully cured by radioiodine.…”