Endocrine Abstracts

Tyrosine kinase inhibitors and other targeted treatments are revolutionizing the treatment of cancer. However multiple endocrine side effects of these treatments are emerging.

Crizotinib, a multi-targeted small molecule tyrosine kinase inhibitor of ALK and c-met, has been approved by the FDA for the treatment of non small cell lung cancer (NSCLC) patients with a novel oncogenic gene fusion, EML4-ALK and its variants. Crizotinib is generally well tolerated. Interestingly, hypogonadism has been observed in patients treated with crizotinib. Weickhardt et al. reduced testosterone level in all NSCLC patients treated with crizotinib compared to only 32% of those not receiving the drug. This occurred as early as 2–3 weeks after treatment initiation with rapid improvement after treatment interruption. The mechanism of crizotinib-induced hypogonadism is unclear with features of both primary and secondary hypogonadism, with some, but not all patients having low gonadotrophins.

We present the case of a 35 years old gentleman with metastatic NSCLC receiving treatment with crizotinib. He described progressive lethargy and loss of libido. Investigations revealed a low testosterone of 5.6 nmol/l and very low SHBG of 8 nmol/l. LH was normal at 4.6 IU/l but FSH was high at 12 IU/l. Prolactin, whilst taking metoclopramide was also elevated but an MRI of his pituitary did not show any evidence of metastases or other pituitary mass.

He therefore appears to have isolated hypogonadism most likely secondary to crizotinib therapy, although the low SHBG has not previously been described with this drug. He has now commenced a trial of testosterone replacement.

This illustrates the importance of endocrinologists being aware of the side effects of novel anti-cancer drugs and of joint working between oncologists and endocrinologists.