Thyroid hormone inactivation in gastrointestinal stromal tumors.
Gastrointestinal stromal tumors (GISTs) are resistant to traditional chemotherapy but are responsive to the tyrosine kinase inhibitors imatinib and sunitinib. The use of these agents has improved the outcome for patients but is associated with adverse effects, including hypothyroidism. Multiple mechanisms of this effect have been proposed, including decreased iodine organification and glandular capillary regression. Here we report the finding of consumptive hypothyroidism caused by marked overexpression of the thyroid hormone-inactivating enzyme type 3 iodothyronine deiodinase (D3) within the tumor. Affected patients warrant increased monitoring and may require supernormal thyroid hormone supplementation.
From the Thyroid Program of the Division of Endocrinology (M.A.M., C.G., C.D., H.S., R.H.J., S.A.H.) and the Clinical Research Center (H.A.F.), Boston Children's Hospital, the Departments of Pathology (A.M.-E., J.A.F., D.M.D., Y.W.), Surgery (C.P.R.), and Radiology (M.C.F.), and the Thyroid Section of the Division of Endocrinology, Diabetes, and Hypertension (L.Y., P.R.L., S.A.H.), Brigham and Women's Hospital, and the Dana-Farber Cancer Institute (J.A.F., C.P.R., P.R.L., S.A.H.) - all in Boston; the Department of Neurobiology and Anatomy, Kochi Medical School, Nankoku, Japan (T.T.); and the Endocrinology and Diabetes Division, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles (J.M.H.).
Michelle A
MA
Maynard
Adrian
A
Marino-Enriquez
Jonathan A
JA
Fletcher
David M
DM
Dorfman
Chandrajit P
CP
Raut
Leila
L
Yassa
Cuicui
C
Guo
Yuexiang
Y
Wang
Clara
C
Dorfman
Henry A
HA
Feldman
Mary C
MC
Frates
Huaidong
H
Song
Rebecca H
RH
Jugo
Takahiro
T
Taguchi
Jerome M
JM
Hershman
P Reed
PR
Larsen
Stephen A
SA
Huang
D005770:Gastrointestinal Neoplasms / Q000150:complications / Q000000981:diagnostic imaging / Q000201:enzymology*; D046152:Gastrointestinal Stromal Tumors / Q000150:complications / Q000000981:diagnostic imaging / Q000201:enzymology*; D006801:Humans; D007037:Hypothyroidism / Q000201:enzymology* / Q000209:etiology*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011860:Radiography, Abdominal; D013963:Thyroid Hormones / Q000172:deficiency*
D013963:Thyroid Hormones; C117274:iodothyronine deiodinase type III; D007453:Iodide Peroxidase