Thyroid Specialists’ LT4+LT3 Prescribing Contradicts Beliefs

TOPLINE:

European thyroid specialists report willingness to prescribe combination levothyroxine (LT4) + liothyronine (LT3) to patients with hypothyroidism who report persistent symptoms even after normalisation of thyroid-stimulating hormone (TSH) levels. These specialists report LT4+LT3 prescribing despite nearly half attributing patients’ persistent symptoms to nonendocrine causes, and the lack of evidence supporting the efficacy and long-term safety of the combination.

METHODOLOGY:

• An online questionnaire survey invitation was sent to 17,247 thyroid specialists in 28 total countries in Europe, the United Kingdom, and Israel, and 32.9% (n = 5695) of specialists responded.

TAKEAWAY:

• Nearly all respondents (98.3%) recommended LT4 as the initial treatment for hypothyroid patients.
• Three-quarters of respondents (75.4%) perceived that the prevalence of persistent hypothyroid-like symptoms despite achievement of normal serum TSH levels with LT4 was ≤ 10% of patients, whereas 42.7% thought that the prevalence was ≤ 5%.
• On a 1-5 Likert scale, 77.1% of the thyroid specialists agreed (grade 4) or strongly agreed (grade 5) that psychosocial factors were a cause of these persistent symptoms, followed by comorbidities (69.2%), patient unrealistic expectations (61.0%), chronic fatigue syndrome (58.5%), and the burden of chronic disease (53.5%).
• Although 42.4% of respondents said they would never prescribe LT4+LT3, others would for the following indications: Persistent symptoms (39.7%), a short period during recovery from protracted hypothyroidism (15.7%), and unexplained weight gain (1.8%).
• In a multivariable analysis, the choice of the LT4+LT3 combination was positively associated with:
  • Being an endocrinologist (odds ratio, 1.44; 95% CI, 1.17-1.76).
  • Having a high-volume practice (1.39; 1.23-1.58).
  • Working in countries with high gross national income per capita (1.021; 1.014-1.027).
• Conversely, the LT4+LT3 combination treatment was negatively associated with:
  • Male respondent (0.86; 0.76-0.97).
  • Working in Western Europe (0.27; 0.20-0.36).

IN PRACTICE:

“About 15% of hypothyroid individuals complain of persistent symptoms despite achieving biochemical euthyroidism on LT4. Evidence from several randomized controlled trials indicates non-superiority of treatment with combination LT4+LT3,” the authors wrote. “[T]here is a need to explore non-pharmacological interventions, such as cognitive behaviour therapy. The finding that most of these hypothyroid-like symptoms are considered non-thyroidal by endocrinologists and yet so many endocrinologists resort to thyroid remedies as a solution is paradoxical and intriguing and merits further in-depth studies,” they added.

SOURCE:

The study was conducted by Roberto Attanasio, of the Scientific Committee Associazione Medici Endocrinologi, Milan, Italy, and colleagues and published online on February 18, 2024, in Thyroid.

LIMITATIONS:

No distinction was made between subclinical and overt hypothyroidism. Virtual patient scenario during the ongoing COVID-19 pandemic. Exclusion of primary care may limit generalisability.

DISCLOSURES:

This research did not receive any financial support. Roberto Attanasio has received support for attending meetings and/or travel from IBSA. Other authors also have industry ties and other disclosures.