Time to reconsider nonsurgical therapy of benign non-toxic multinodular goitre: focus on recombinant human TSH augmented radioiodine therapy

Abstract

The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in large compressive goitres. While some patients decline surgery others may have contraindications due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are needed. Until recently, levothyroxine therapy was the preferred non-surgical alternative, but due to low efficacy and potential side-effects, it is not recommended for routine use in recent international guidelines. Conventional radioiodine ( 131 I) therapy has been used for two decades as an effective and safe alternative to surgery in the treatment of symptomatic non-toxic MNG. Since much higher activities of 131 I are employed when treating non-toxic rather than toxic MNG, there has been reluctance in many countries to use this treatment modality. Frequently, the 131 I -uptake in a non-toxic MNG is low, which makes 131 I therapy less feasible. Another challenge is the negative correlation between the initial goitre size and goitre volume reduction (GVR). With its ability to more than double the thyroid 131 I-uptake, recombinant human TSH (rhTSH) increases the absorbed radiation dose and thus enhances the GVR by 35-56% at the expense of up to fivefold higher rate of permanent hypothyroidism. An alternative strategy is to reduce the administered 131 I-activity with a factor corresponding to the rhTSH induced increase in 131 I-uptake. Hereby, the extrathyroidal irradiation can be reduced without compromising efficacy. Thus, although in its infancy, and still experimental, rhTSH-augmented 131 I therapy may profoundly alter the non-surgical treatment of benign non-toxic MNG.

Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter

“…In another paper, a dose of 0.2 mg was administered twice in euthyroid patients, resulting in temporary overt hyperthyroidism lasting 14 days, which is not desirable in elderly patients, particularly ones with concomitant circulatory disorders [25]. Consequently, the authors suggest routine preventive symptomatic treatment [25,31,44]. Studies with patients aged 42-80 years showed that a single dose of 0.1 mg of rhTSH induces hyperthyroidism, which increases the risk of left-sided diastolic heart failure three times [45].…”

Változások a pajzsmirigybetegségek radiojódkezelésében

“…Áttörést jelentett az utóbbi években a rekombináns humán tireotropin (rhTSH) alkalmazása: igen hatéko-nyan növeli a jódfelvételt és más kedvező hatásai is vannak [30]. Megváltoztatja a mikrodozimetriát, a kevésbé aktív, "dormant" folliculus sejtek aktívabbá válnak, homogénebbé válik a jódfelvétel.…”

“…Előnyösen változik a jódki-netika, emiatt az extrathyreoidealis sugárterhelés csök-ken. A fentiek eredményeképpen a pajzsmirigyvolumen nagyobb mértékben csökken, mint a konvencionális terápiánál [30]. Utóbbinál a strúma nagysága és a volumencsökkenés fordított korrelációt mutat, rhTSH-val ez megfordul: minél nagyobb a volumen, annál kedvezőbb a terápiás hatás, a volumencsökkenés.…”

THERAPY OF ENDOCRINE DISEASE: Recombinant human TSH and radioactive iodine therapy in the management of benign multinodular goiter

“…Pretreatment with methimazole before 131 I therapy for TMNG is indicated in patients who are at an increased risk for complications due to worsening of hyperthyroidism, including elderly and those with cardiovascular disease or severe hyperthyroidism (35). rhTSH can at least double thyroid RAIU (12,18,36,37,38), depending on the baseline RAIU, and it determines a more homogeneous distribution of 131 I in MNG (22). During the last decade, and based on the above observations, rhTSH has been evaluated as an adjuvant to 131 I therapy, in an attempt to improve the efficacy of this treatment for MNG (18,39,40).…”

“…The administration of recombinant human thyrotropin (rhTSH) before 131 I has been shown to be a potentially valuable therapeutic tool for the management of MNG (11,12,13,14,15,16,17,18,19,20). rhTSH in a low single dose increases 131 I uptake by two-to fourfold, and similar therapeutic effects (in comparison with higher 131 I activities without rhTSH prestimulation), and with lower exposure of extrathyroidal tissues to radiation (23 given (11,14,16,19,24,25).…”