Total thyroid ablation in Graves’ orbitopathy

Abstract

Graves' orbitopathy (GO) is an autoimmune condition almost always associated with autoimmune thyroid disease, especially Graves' disease (GD). According to the most widely accepted model, the autoantigens responsible for GO would include molecules expressed by thyroid epithelial cells that are present also in orbital tissues. The high likelihood that the etiologies of GO and of the underlying autoimmune thyroid diseases are somehow linked is confirmed by the very close relationship between GO, the onset and the course of Graves' diseases, the size of the thyroid gland, and most importantly, thyroid function and thyroid treatment. Based on these considerations, it has been proposed that complete removal of thyroid antigens and of thyroid infiltrating lymphocytes, the so-called total thyroid ablation (TTA), may be followed by an attenuation of the immune reaction against orbital antigens, and ultimately by an amelioration of GO. The possibility that TTA, achieved by near total thyroidectomy followed by radioiodine, may be beneficial for GO was initially suggested by two retrospective studies and more recently by two prospective, randomized clinical trials conducted in patients with moderate GO treated with intravenous glucocorticoids. Although there seemed to be no difference in the long term, compared with near total thyroidectomy alone TTA was associated with a shorter time required for GO to improve, or anyway to reach its best possible outcome, and with a lesser requirement for additional treatments for GO to improve. Whether this is sufficient to offer ablation to patients remains a matter of discussion. At present, this procedure could be offered only to patients scheduled to thyroidectomy and glucocorticoid treatment.

Occurrence of Graves’ Orbitopathy and Graves’ Hyperthyroidism after a Trauma to the Eye

“…Coupled with our observation, these reports support the hypothesis that an eye trauma and the subsequent spreading of autoantigens may be responsible for the de novo appearance or deterioration of GO, which is in line with the autoimmune nature of the eye disease. In our case, the subsequent development of hyperthyroidism is very much in keeping with the hypothesis that GH and GO are due to autoimmunity against autoantigens present both in the thyroid and in orbital tissues [5, 6]. Of course, we cannot prove that there was a direct cause-effect relationship between the eye trauma and the occurrence of GO and GH in our patient.…”

“…The idea is that a trauma may cause a tissue damage, with subsequent spreading of autoantigens, which in a predisposed individual – our patient had a familial history of thyroid autoimmunity – may trigger autoimmunity against these antigens, thereby precipitating GO first and then GH, the latter due to the very high likelihood that the two conditions reflect autoimmunity against antigens shared by the thyroid and orbital tissues [5, 6]. …”

“…The association between GO and thyroid autoimmunity, as well as the influence of the underlying thyroid disease and its treatment on GO [1-4], suggest a close relationship between the thyroid gland and the affected orbital tissues [5]. Thus, most investigators believe that GO is the consequence of autoimmunity against antigens that are present both in the thyroid and in orbital tissues [6]. In this regard, massive release of thyroid antigens is believed to cause the appearance or deterioration of GO in patients with GH, as it occurs following radioiodine treatment, unless a glucocorticoid prophylaxis is given [7, 8].…”

Quale trattamento attuare per l’ipertiroidismo nei pazienti con orbitopatia basedowiana?

“…Il termine ablazione tiroidea totale indica un impiego sequenziale della terapia chirurgica e di quella radiometabolica, come comunemente si attua nei pazienti affetti da carcinoma tiroideo. L'idea sottesa a questo approccio è che, con questa terapia combinata, si potrebbe ottenere una completa rimozione dei linfociti T tiroidei autoreattivi e degli antigeni tiroidei, interrompendo, in questo modo, il link tra tiroide e orbita che è alla base della patogenesi dell'orbitopatia e attenuando la risposta autoimmune contro antigeni orbitari [6].…”

“…Una linea di pensiero sostiene che in questi pazienti si debba dare la priorità al trattamento dell'orbitopatia e rimandare l'eventuale terapia definitiva dell'ipertiroidismo finché l'orbitopatia sarà stata completamente inattivata e curata (con la terapia farmacologica e/o chirurgica [12]. Una seconda linea di pensiero suggerisce che, in considerazione del link patogenetico tra tiroide e orbita, sarebbe preferibile ablare la tiroide con la terapia chirugica o radiometabolica o, meglio, con una combinazione delle due (ablazione tiroidea totale) [6]. Questo tipo di approccio avrebbe il vantaggio di rimuovere i linfociti T autoreattivi e gli antigeni tiroidei responsabili dell'innesco, a livello orbitario, delle reazioni autommuni che, attraverso la conseguente cascata di eventi (proliferazione dei fibroblasti, espansione del tessuto adiposo, secrezione di citochine, infiltrazione dei muscoli extraoculari, aumentata produzione di glicosaminoglicani), portano allo sviluppo delle manifestazioni cliniche dell'orbitopatia [6].…”