Journal Article

Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma

Thomas J Giordano, Bryan R Haugen, Steven I Sherman, Manisha H Shah, Elaine M Caoili and Ronald J Koenig

in The Journal of Clinical Endocrinology & Metabolism

Volume 103, issue 4, pages 1277-1281
ISSN: 0021-972X
Published online January 2018 | e-ISSN: 1945-7197 | DOI: https://dx.doi.org/10.1210/jc.2017-02533
Pioglitazone Therapy of PAX8-PPARγ Fusion Protein Thyroid Carcinoma

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  • Medicine and Health
  • Clinical Medicine
  • Endocrinology and Diabetes
  • Medical Oncology
  • Reproductive Medicine

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Abstract

Context

A subset of thyroid carcinomas expresses an oncogenic paired box 8 (PAX8) and peroxisome proliferator activated receptor γ (PPARγ) fusion protein (PPFP). The PPARγ/PPFP ligand pioglitazone is highly therapeutic in a transgenic mouse model of PPFP thyroid carcinoma, but whether pioglitazone is therapeutic in patients with PPFP thyroid carcinoma is unknown.

Case Description

Tumor blocks from 40 patients with progressive thyroid cancer despite standard-of-care therapy were screened for PPFP, and the tumor from only one patient (2.5%) was positive. The patient had a 6.0-cm acetabular soft tissue metastasis from Hürthle cell carcinoma that caused severe pain on weight bearing and had a serum thyroglobulin level of 1974 ng/mL. After 24 weeks of therapy with pioglitazone, the metastatic lesion was 3.9 cm, the thyroglobulin level was 49.4 ng/mL, and the patient was pain-free. Thirteen months after discontinuation of pioglitazone, the metastatic lesion was 3.6 cm, the thyroglobulin level was 4.7 ng/mL, and the patient remained pain-free.

Conclusions

Pioglitazone may be therapeutic in patients with PPFP thyroid cancer. However, thyroid cancers that are progressive despite standard-of-care therapy appear to only rarely express PPFP.

Journal Article.  2472 words.  Illustrated.

Subjects: Medicine and Health ; Clinical Medicine ; Endocrinology and Diabetes ; Medical Oncology ; Reproductive Medicine

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