Endocrine Abstracts

Background: Levothyroxine (LT4) monotherapy is the mainstay of treatment of hypothyroidism, but a sizeable minority of endocrinologists also use T3-containing treatments in some patients notwithstanding concern about their safety.

Methods: 17,247 thyroidologists from 28 countries were invited to participate in a questionnaire survey. Geographic regions were defined according to the UN Statistics Division. Gross national income (GNI) information stems from https://data.worldbank.org/.

Findings: The response rate was 32.9%. LT4 was the initial treatment chosen by the majority (98.3%). Other options favored by a minority were: LT4 + LT3 1.2%; LT3 monotherapy 0.3%; desiccated thyroid extracts (DTE) 0.1%. A significant minority (42.4%) of respondents stated that they would never consider LT4 + LT3 combination treatment. LT4 + LT3 combination treatment was favored by 39.7% for patients with persistent symptoms, by 15.7% for a short period in patients recovering from protracted hypothyroidism. Multivariate analysis showed that LT4 + LT3 combination treatment was positively associated with a) being an endocrinologist compared to other specialties (OR 1.44; 95% CI 1.17-1.76); b) having a high-volume compared to low volume practice (OR 1.39; 95% CI 1.23-1.58); c) and working in countries with high compared to low GNI (OR 1.021; 95% CI 1.014-1.027). Conversely LT4 + LT3 combination treatment was negatively associated with a) respondent being male (OR 0.86; 95% CI 0.76-0.97), and b) working in Western Europe compared to other regions (OR 0.27; 95% CI 0.20-0.36). In addition, choice of T3-containing medication was significantly associated with respondents’ view that LT4 alone cannot restore normal physiology and inversely associated with the view that patients’ unrealistic expectations are the cause of persisting symptoms.

Interpretation: The vast majority of respondents considered LT4 as the first line of treatment, while a very small minority (1.7%) chose T3-containing treatments. The THESIS respondents’ approach to LT3-containing treatments is in accordance with present evidence. Nearly all respondents stated that they would not use LT4 + LT3 combination as initial treatment, and only 40% would consider this therapy for persistent symptoms. Why this treatment option was more frequently recommended by endocrinologists who work in private practice, who are female, and who live in countries with higher GNIPC is unclear and requires further study. At variance with reports from the USA, DTE was nearly never recommended by THESIS respondents. This may reflect concerns about overtreatment, unphysiological fluctuations in T3 levels and variable potency and is consistent with available evidence and recommendations by professional guidelines.