tiro id ma mi

REVIEW Time to reconsider nonsurgical therapy of benign non-toxic multinodular goitre: focus on recombinant human TSH augmented radio iodine therap y Søren Fast, Viveque Egsgaard Nielsen, Steen Joop Bonnema and Laszlo Hegedu ¨ s Department of Endocrinology and Metabolism, Odense University Hospital, DK-5000 Odense C, Denmark (Correspondence should be addressed to S Fast; Email: [email protected]) Abstract The treatment of benign multinodular goitre (MNG) is controversial, but surgery is recommended in largecompress ivegoitres . Whilesome patie nts declin e surge ry others mayhave contr aindication s due to comorbidity, since MNG is prevalent in the elderly. Therefore, non-surgical treatment alternatives are neede d. Until rece ntly, levoth yrox ine thera py was the prefe rred non-s urgic al al ternat ive, but due to l ow effica cy and poten tial side-eff ects, it is not recomme nded for routine use in recent internation al guidel ines.Conventiona l radio iodine( 131 I)thera py hasbeenused fortwo decades asaneff ect iv e andsafe 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 ther apy less feasible. Anot her chal lenge is the nega tiv e correlat ion between the initia l goitr e size and goitre volume reduction (GVR). With its ability to more than double the thyroid 131 I-uptake, rec omb inant human TSH(rhTS H) inc reasesthe absor bedradiat ion dos e and thu s enh anc es theGVR 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. European Journal of Endocrinology 160 517–528 Introduction Desp ite iod ization programme s, simple goitr e – defin ed as a euthyroid goitre that is not associated with thyroid autoimmunity or malignancy – still constitutes a major diagno stic and therap eutic challenge . Such goitres can be dif fuse , uni- or mul tinodular (1). When app lying ultrasound (US), most goitres have a nodular structure, part icularl y in the elderl y (1). Acco rdin g to curre nt thi nkin g, the y are caused by an interaction bet we en genetic susceptibility and en vironmental triggers, iodine deficiency being the most important. There is no ideal tre atment for benign mul tinodular go itre (MNG), as refle cte d by the lac k of consensus in questio nnaire surveys (2–5). Surgery is recommended when facing a large goitre or when malignancy cannot be ruled out (6, 7) . However , it is importa nt to rec ogn ise that a considerable proportion of patients refuse surgery, even in the conte xt of a lar ge sympto mat ic go itr e, whi ch underlines the need for non-surgical alternatives. The non-surgical treatment opt ions are: iodine supplementation, levothyroxine (LT 4 ) therapy and radioiodine ( 131 I) therap y . In theory , percut aneous interv entiona l therapy (laser photocoagulation or ethanol injection) is also an option in MNG, but so far it is only experimental and nocontrolle d studie s exi st. At bes t, LT 4 the rapy has a minor effect on the appearance of new nodules but does not shrink the existing nodules (8). Due to low efficacy and accumula ting evidence of cardiovascular and skeletal side-effects, it is not recommended for routine use in recent guid elin es (6, 9) and reviews (7, 10). Iod ine supplementation therapy is not superior to LT 4 therapy and a maj or hind rance is the potential inductio n of hyperthyroidism (11). Conv entiona l (witho ut rhTSH) 131 I therapy has been used for more than a decade in symptomat ic non-toxic MNG, result ing in a mean thyroid vol ume reduction of w40% 1 year after treatment (12) and 50–60% after 3–5 ye ars (13). Genera lly , patie nt satisfa ction is high and sympt oms are considerably improved (14). A major drawback of this therapy is the need for relatively high activities of radioiodine when treating large goitres. Furthermore, the effect is attenuated with increasing goitre size (15). Ano ther chal lenge is the fre quent findi ng of a low (belo w 20%) thyroid radioiodine uptake (RAIU), caused mainly European Journal of Endocrinology (2009) 160 517–528 ISSN 0804-4643 q 2009 European Society of Endocrinology DOI: 10.1530/EJE-08-0779 Online version via www.eje-online.org

tiro id ma mi

Documents