Sorafenib-induced hypothyroidism is associated with increased type 3 deiodination.
BACKGROUND
Therapy with tyrosine kinase inhibitors is associated with thyroid dysfunction. Decreased serum thyroid hormone levels during tyrosine kinase inhibitors are also observed in athyreotic patients with thyroid carcinoma. We therefore hypothesized that tyrosine kinase inhibitors may influence thyroid hormone metabolism.


OBJECTIVE
The aim was to study the effects of sorafenib therapy on serum thyroid hormone concentrations and iodothyronine deiodination in athyreotic patients.


METHODS
The design included a prospective open, single-center, single-arm 26-wk study.


METHODS
We measured serum thyroxine (T4), free T4, 3,5,3-triiodothyronine (T3), free T3, reverse T3 (rT3), and TSH concentrations at baseline and after 26 wk in 21 patients with progressive nonmedullary thyroid carcinoma treated with sorafenib. Ratios of T3/T4 and T3/rT3, which are independent of substrate availability and reflect iodothyronine deiodination, were calculated.


RESULTS
Serum free T4 and T3 levels, adjusted for levothyroxine dose per kilogram body weight, decreased by 11 and 18%, respectively, whereas TSH levels increased. The serum T3/T4 and T3/rT3 ratios decreased by 18 and 22%, respectively, which is compatible with increased type 3 deiodination.


CONCLUSIONS
Sorafenib enhances T4 and T3 metabolism, which is probably caused by increased type 3 deiodination.
Abdulrahman
Randa M
RM
Department of Endocrinology, C4-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
Verloop
Herman
H
Hoftijzer
Hendrieke
H
Verburg
Erik
E
Hovens
Guido C
GC
Corssmit
Eleonora P
EP
Reiners
Christoph
C
Gelderblom
Hans
H
Pereira
Alberto M
AM
Kapiteijn
Ellen
E
Romijn
Johannes A
JA
Visser
Theo J
TJ
Smit
Johannes W
JW
D000368:Aged; D000369:Aged, 80 and over; D001557:Benzenesulfonates / Q000009:adverse effects* / Q000627:therapeutic use; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011725:Pyridines / Q000009:adverse effects* / Q000627:therapeutic use; D000077157:Sorafenib; D013964:Thyroid Neoplasms / Q000097:blood / Q000188:drug therapy*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood* / Q000627:therapeutic use; D016896:Treatment Outcome; D014284:Triiodothyronine / Q000097:blood*
D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014284:Triiodothyronine; D009536:Niacinamide; D013972:Thyrotropin; D000077157:Sorafenib; D013974:Thyroxine