Association between L-thyroxine treatment, GH deficiency, and radiological vertebral fractures in patients with adult-onset hypopituitarism

Objective: In this study, we aimed at evaluating the association between radiological vertebral fractures and levo-thyroxine (L-T-4) replacement doses in adult patients with hypopituitarism. Design: Cross-sectional study. Methods: We studied 74 adult hypopituitary patients (males, 43; females, 31; mean age, 57 years; and range, 23-79) with central hypothyroidism treated with L-T4 (median daily dose: 1.1 mu g/kg). All patients also had severe GH deficiency (GHD) and 38 of them were replaced with recombinant GH. Vertebral fractures were assessed by a quantitative morphometric analysis performed on thoracic and lumbar spine lateral X-ray. Results: Radiological vertebral fractures were found in 23 patients (31.1%) in association with untreated GHD (P=0.02), higher serum free T4 levels (P=0.03), a higher daily dose of L-T4 (P=0.005), and a longer duration of hypopituitarism (P=0.05). When GHD was treated, the prevalence of vertebral fractures was more frequent (P=0.03) in patients receiving high L-T4 doses (third tertile: >1.35 pig/kg per day) as compared with patients who were treated with lower drug doses (first tertile: <0.93 pig/kg per day). Such a difference was not observed in patients with untreated GHD who showed a higher prevalence of vertebral fractures regardless of L-T4 daily doses. Multivariate analysis showed that untreated GHD (odds ratio: 4.27, 95% Cl 1.27-14.33; P=0.01) and the daily dose of L-T4 (odds ratio: 4.01, 95% Cl 1.16-14.39; P=0.03) maintained a significant and independent association with vertebral fractures in patients with central hypothyroidism. Conclusions: Our data suggest for the first time that a relative overtreatment with L-T4 may influence the fracture risk in some patients with hypopituitarism.