Scoping Review Links Stronger TSH Suppression to Skeletal Harm in Thyroid Cancer

This scoping review, reported according to PRISMA-ScR and prospectively registered, examined patient-, treatment- and disease-related factors associated with adverse effects of postoperative TSH-directed levothyroxine therapy in adults with differentiated thyroid cancer. The authors searched MEDLINE, Embase and Cochrane CENTRAL for studies published from January 2011 to February 2026. Of 7,361 records screened, 35 studies including 11,819 patients were included; findings were synthesized descriptively and narratively.

Skeletal outcomes were reported most often (51.4% of studies), followed by cardiometabolic outcomes (40.0%). Greater suppression intensity was the most consistent treatment-related factor associated with skeletal adverse outcomes, particularly in studies assessing subnormal TSH. Longer treatment duration was associated with skeletal harm in some studies, and postmenopausal status emerged as a relatively consistent patient-level factor. Findings for age and body mass index varied. Evidence concerning other outcome categories was less extensive and less consistent; only two studies assessed prediction or discrimination, both for skeletal outcomes.

The review highlights the need to balance potential oncologic benefit against treatment-related harm, but it does not establish individual risk estimates or support a specific change in TSH targets. Exposure definitions varied substantially, and evidence for clinically applicable toxicity prediction and cumulative treatment burden remains limited.