Roberto Cirocchi, Stefano Trastulli, Justus Randolph, Salvatore Guarino, Giorgio Di Rocco, Alberto Arezzo, Vito D'Andrea, Alberto Santoro, Marcin Barczyñski, Nicola Avenia

Total thyroidectomy (TT) and subtotal thyroidectomy (ST) are worldwide treatment options for multinodular non-toxic goitre in adults. Near TT, defined as a postoperative thyroid remnant less than 1 mL, is supposed to be a similarly effective but safer option than TT. ST has been shown to be marginally safer than TT, but it may leave an undetected thyroid cancer in place. The objective was to assess the effects of total or near-total thyroidectomy compared to subtotal thyroidectomy for multinodular non-toxic goitre. We searched the Cochrane Library, MEDLINE, PubMed, EMBASE, as well as the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 18 June 2015 for all databases. No language restrictions were applied. Two review authors independently scanned the abstract, title or both sections of every record retrieved to identify randomised controlled trials (RCTs) on thyroidectomy for multinodular non-toxic goitre for further assessment. Two review authors independently extracted data, assessed studies for risk of bias and evaluated overall study quality utilising the GRADE instrument. We calculated the odds ratio (OR) and corresponding 95% confidence interval (CI) for dichotomous outcomes. A random-effects model was used for pooling data. We examined 1430 records, scrutinized 14 full-text publications and included four RCTs. Altogether 1305 participants entered the four trials, 543 participants were randomised to TT and 762 participants to ST. A total of 98% and 97% of participants finished the trials in the TT and ST groups, respectively. Two trials had a duration of follow-up between 12 and 39 months and two trials a follow-up of 5 and 10 years, respectively. Risk of bias across studies was mainly unknown for selection, performance and detection bias. Attrition bias was generally low and reporting bias high for some outcomes. In the short-term postoperative period no deaths were reported for both TT and ST groups. However, longer-term data on all-cause mortality were not reported (1284 participants; 4 trials; moderate quality evidence). Goiter recurrence was lower in the TT group compared to ST. Goiters recurred in 0.2% (1/425) of the TT group compared to 8.4% (53/632) of the ST group (OR 0.05 (95% CI 0.01 to 0.21); P < 0.0001; 1057 participants; 3 trials; moderate quality evidence). Re-intervention due to goitre recurrence was lower in the TT group compared to ST. Re-intervention was necessary in 0.5% (1/191) of TT patients compared to 0.8% (3/379)of ST patients (OR 0.66 (95% CI 0.07 to 6.38); P = 0.72; 570 participants; 1 trial; low quality evidence). The incidence of permanent recurrent laryngeal nerve palsy was lower for ST compared with TT. Permanent recurrent laryngeal nerve palsy occurred in 0.8% (6/741) of ST patients compared to 0.7% (4/543) of TT patients (OR 1.28, (95% CI 0.38 to 4.36); P = 0.69; 1275 participants; 4 trials; low quality evidence). The incidence of permanent hypoparathyroidism was lower for ST compared with TT. Permanent hypoparathyroidism occurred in 0.1% (1/741) of ST patients compared to 0.6% (3/543) of TT patients (OR 3.09 (95% CI 0.45 to 21.36); P = 0.25; 1275 participants: 4 trials; low quality evidence). The incidence of thyroid cancer was lower for ST compared with TT. Thyroid cancer occurred in 6.1% (41/669) of ST patients compared to 7.3% (34/465)of TT patients (OR 1.32 (95% CI 0.81 to 2.15); P = 0.27; 1134 participants; 3 trials; low quality evidence). No data on health-related quality of life or socioeconomic effects were reported in the included studies. The body of evidence on TT compared with ST is limited. Goiter recurrence is reduced following TT. The effects on other key outcomes such as re-interventions due to goitre recurrence, adverse events and thyroid cancer incidence are uncertain. New long-term RCTs with additional data such as surgeons level of experience, treatment volume of surgical centres and details on techniques used are needed.