Endocrine Abstracts

Case history: A 72 year old male was diagnosed with primary lung adenocarcinoma grade T4N2M1b with adrenal and brain metastasis 1 year previously. On diagnosis his tumour was strongly positive for PDL-1 expression. This patient was started on dexamethasone 8 mg once a day that was weaned down to 4mg twice daily and then slowly weaned off steroids whilst receiving whole brain radiation. He was started on pembrolizumab therapy and had received ten cycles of treatment when he began experiencing worsening headaches and generalised malaise. He was referred to the endocrinology team with a 0900 h cortisol level of 33 nom/l, TSH 0.34 miU/l, fT3 2.9 pmol/l and fT4 10.9 pmol/l; with a rising prolactin and low testosterone count. This acute change in his pituitary function was likely associated with pembrolizumab. Since this diagnosis he has been treated with levothyroxine and hydrocortisone and his pembrolizumab therapy was held for review.

Investigations: Initial investigations by the oncology team revealed a 9am cortisol level of 135 nmol/l, fT4 16 pmol/l and TSH 0.46 miu/l pre-initiation of pembrolizumab. After cycle ten prolactin level went from 320 mu/l to 1085 mu/l, 0900 h cortisol level of 33 nmol/l, fT4 10.4 pmol/l and TSH 0.23 miu/l Testosterone 5.3 nmol/l, sex hormone binding globulin 79 nmol/l, free androgen index 6.7, ILGF-1 was 15.6 nmol/l. CT head and MRI head showed multiple frontal lobe metastasis with no pituitary involvement and CT abdomen confirmed steady disease in left adrenal metastasis. Visual fields remained intact in this patient and he had no changes in his blood pressure control.

Results and treatment: Symptoms improved on 125 micrograms of levothyroxine and hydrocortisone (20 mgs in the morning and 10 mg in the evening). Thyroid function improved and his levothyroxine was weaned. He remains on hydrocortisone replacement. Initially his pembrolizumab therapy was held and after 3 weeks it was restarted. Current prolactin is 1305 mu/l and testosterone remains low.

Conclusions and points for discussion: <0.1% of those on pembrolizumab suffer from endocrinopathies. The level of adverse effects does not correlate with the number of treatment cycles. Predicting endocrinopathies is difficult in practice and requires regular monitoring. Pembrolizumab improves prognosis and in our opinion hypophysitis should not deem a patient unsuitable for further treatment. An important differential is pituitary metastasis. Testosterone replacement and treating hyperprolactinemia should be reviewed.