Complete resolution of hypercortisolism with sorafenib in a patient with advanced medullary thyroid carcinoma and ectopic ACTH (adrenocorticotropic hormone) syndrome.
BACKGROUND
The treatment of advanced medullary thyroid carcinoma (MTC) has evolved significantly over the past decade. The discovery of genetic abnormalities in MTC has led to the development of targeted therapies such as vandetanib and cabozantinib. Other kinase inhibitors (KI), such as sorafenib, have been investigated in this setting and are an alternative therapeutic option. The lack of specificity of these KIs to a single target may result in additional, unexpected effects. In this report, we describe a patient with metastatic MTC and Ectopic ACTH (adrenocorticotropic hormone) Syndrome in whom treatment with sorafenib resulted in complete resolution of hypercortisolism.


CONCLUSIONS
A 45-year-old male with progressive metastatic MTC presented with clinical manifestations suspicious for Cushing's syndrome. Investigation revealed ACTH-dependent hypercortisolism suggestive of Ectopic ACTH Syndrome. Treatment with sorafenib 400 mg twice a day was initiated resulting in a rapid and significant reduction of cortisol and ACTH levels associated with dramatic clinical improvement. The rapid and effective control of hypercortisolism in the absence of a significant tumor reduction raises the question of whether sorafenib may have a direct effect on ACTH or cortisol hypersecretion.


CONCLUSIONS
This report suggests a previously unknown potential effect of sorafenib on the pituitary-adrenal axis. Further studies will be necessary to investigate the role of sorafenib in other cases of ACTH excess and to understand the mechanisms by which it alters steroid synthesis, action, or secretion.
1 Department of Medical Oncology, Instituto do Câncer do Estado de São Paulo (ICESP) , São Paulo, Brazil .
Romualdo
R
Barroso-Sousa
Antonio Marcondes
AM
Lerario
Joao
J
Evangelista
Carla
C
Papadia
Delmar M
DM
Lourenço
Chin Shien
CS
Lin
Marco Antonio
MA
Kulcsar
Maria Candida
MC
Fragoso
Ana O
AO
Hoff
D000182:ACTH Syndrome, Ectopic / Q000188:drug therapy*; D018278:Carcinoma, Neuroendocrine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D010913:Pituitary-Adrenal System / Q000187:drug effects; D000077157:Sorafenib; D013964:Thyroid Neoplasms
D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib