PRIMARY ADRENAL INSUFFICIENCY DURING LENVATINIB OR VANDETANIB AND IMPROVEMENT OF FATIGUE AFTER CORTISONE ACETATE THERAPY.

UNASSIGNED

Two tyrosine kinase inhibitors (TKIs), Lenvatinib and Vandetanib, are frequently used for the treatment of advanced radioiodine refractory differentiated thyroid cancer (RAI-R DTC) and medullary thyroid cancer (MTC), respectively. Fatigue is a frequent adverse event during treatment with these and other tyrosine-kinase inhibitors, and a common cause of drug discontinuation or dose reduction.

UNASSIGNED

We evaluated the basal and stimulated adrenal function in 12 patients with advanced RAI-R DTC and MTC treated with Lenvatinib or Vandetanib, respectively. Ten patients complaining of fatigue showed a progressive ACTH increase with normal cortisol levels. Moreover, 6/10 patients had a blunted cortisol response after ACTH stimulation, thus confirming the diagnosis of primary adrenal insufficiency (PAI). The causality relationship between TKIs and PAI onset was also demonstrated by the repeated testing of the adrenal function before and during treatment. Patients with PAI received cortisone acetate (CA) replacement therapy, with a significant and prompt improvement in the degree of fatigue, as assessed by the CTCAE Version 4.03, thus supporting the major impact of the impaired adrenal function in the genesis of this adverse event.

UNASSIGNED

We show for the first time that the occurrence of PAI may be a frequent cause of fatigue during Lenvatinib and Vandetanib treatment, and we thus recommend testing adrenal function for a prompt start of replacement therapy in order to avoid discontinuation of treatment or dose reduction, as well as potentially severe PAI complications.