Endocrine Abstracts

Case history: A patient with malignant melanoma with multiple cerebral metastases and a left adrenal metastasis was treated with CRT (30Gy, 10 fractions). This was followed by 12 cycles of Nivolumab, after which the left adrenal lesion was managed with cyberknife (30Gy, three fractions) and Nivolumab was continued thereafter. The patient developed worsening deafness, became unsteady on his feet and complained of feeling generally unwell. At this time an MRI brain was performed showing increased signal intensity in the deep white matter, which was thought to be subsequent to the radiation. The patient was commenced on steroids at this time, though they were later withdrawn due to intolerable effects of mood instability. The patient was referred to for an endocrinology opinion 2 years after the CRT and Nivolumab treatment commenced, as the patient was feeling increasingly fatigued, had lost around 10 kg in weight and had begun experiencing gait and balance abnormalities. He also described reduction in libido, lack of erections and increasing gynaecomastia.

Investigations: 0900 h blood results:

Cortisol 62 nmol/l, ACTH 8 pg/l

Testosterone 2 nmol/l, LH 2, FSH 5

T4 6.2 pmol/l, THS 3.42 nU/l

Prolactin 250 mU/ml

Imaging: MRI showed stable appearances of the known cerebral metastases and no pituitary abnormality.

Results and treatments: Commenced on 5 mg prednisolone OD, levothyroxine 75 μg OD, and testogel, with significant symptomatic improvement.

Conclusions and points for discussion: Both cranial radiotherapy and nivolumab have effects on the pituitary. Pituitary abnormalities after radiotherapy depend on the dose and duration, with growth hormone deficiency being most common. Pan-hypopituitartism would be unusual 2 years after 30Gy to the whole brain. Nivolumab is a monoclonal IgG that blocks Programmed Death Receptor 1 (PD1 Ab) and has shown activity in multiple cancers. Whilst the CTLA-4 inhibitor causes pan-hypopituitarism in up to 20% of patients, nivolumab only affects the pituitary in about 1 in 1000 and then usually results in isolated ACTH deficiency. Therefore this case is unusual, and we hypothesis that the prior radiotherapy may have modified the immune mediated effects of nivolumab, perhaps by inducing neo-antigen expression in the pituitary.