Journal des troubles thyroïdiens et de la thérapie
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Effect of Pioglitazone on Thyroid Hormones and IGF-I in Patients with Type 2 Diabetes

Lisa Arnetz, Mikael Lantz, Kerstin Brismar, Neda Rajamand Ekberg, Michael Alvarsson and Mozhgan Dorkhan

Background: Thyroid hormones induce insulin resistance. Pioglitazone is a peroxisome proliferator activated receptor gamma (PPARγ) agonist, used as treatment of type 2 diabetes (T2D) to increase insulin sensitivity. PPARs and thyroid hormone receptors (TRs) induce intracellular effects through similar molecular mechanisms, and the former may inhibit activation of the latter. Pioglitazone has been shown to increase eye protrusion, a symptom linked both to disturbed thyroid hormone levels and orbital edema secondary to increased IGF-I.

Aims: We investigated whether attenuation of insulin resistance with pioglitazone affects thyroid hormone status and IGF-I.

Methods: 48 patients with T2D were treated with pioglitazone for 26 weeks. Thyroid hormones and IGF-I were analyzed before and after treatment.

Results: After treatment, decreased free T4 decreased (from 14.2+0.4 to 13.3+0.3 pmol/L, p=0.009) and TSH increased (from 190+200 to 220+200 U/L, p = 0.004). IGF-I also increased (from 0.5 ± 0.2 to 1.0 ± 0.2 SD, p<0.001).

Conclusion: Pioglitazone lowers free T4 and increases IGF-I in T2D. This may be due to impeded activation of the TR due to PPAR activation. Increased TSH is most likely secondary to reduced T4. Increased IGF-I may cause orbital edema, as previously noted in patients treated with pioglitazone.