Endocrine Abstracts

Case history: A 57 year old man is referred due to repeated admissions with confusion, malaise, hypotension and hyponatraemia. He has a background of metastatic melanoma (brain, liver, lung) for which he had received surgery, whole brain radiotherapy and combined immunotherapy (Ipilimumab and Nivolumab). At the time of referral he was on a maintenance regimen of Nivolumab, the dose of which had been increased just prior to the aforementioned admissions. There was no past medical history of note nor any family history of endocrinopathies.

Investigations: Sodium ranged between 133 to 145 mmol/L prior to the increase in Nivolumab, afterwards it declined to a nadir of 125 mmol/L (at which point the urine osmolality was 361 mmol/kg and urine sodium was 80 mmol/L). Potassium remained within normal range throughout these episodes, as did his eGFR. Short synacthen results: Cortisol 76, 196, 274 mmol/L (time zero, 30 mins and 60 mins, respectively). ACTH15 ng/L TSH 1.08 mU/L, FreeT4 8.5 pmol/L, FreeT3 2.1 pmol/L LH 5.9 IU/L, FSH 11.9 IU/L, Testosterone 14.0 nmol/L, SHBG 72 nmol/L, Free Testosterone (calculated) 158 pmol/L, Prolactin 22 mIU/L MRI pituitary: Isointense/high T1 3 mm nodule behind the attachment of the pituitary stalk with enhancement of the pituitary stalk. High T1 nodules, three in the right temporal lobe, one in left posterior putamen and one in right medial thalamus in keeping with known brain metastases. Historic CT chest and abdomen: No evidence of adrenal abnormality.

Results and treatment: Following the short synacthen results he was initiated on the replacement dose of hydrocortisone (10 mg, 5 mg, 5 mg). This led to a prompt and profound improvement in his symptoms and sodium. Following the receipt of the ACTH result he was started on levothyroxine (50 mcg once daily). The Nivolumab was continued according to the schedule.

Conclusions and points for discussion: Melanoma rarely metastasizes to the pituitary gland, however the MRI appearance in the context of this patient, is suggestive. Given the site of the lesion, we would have expected hyperprolactinaemia.

Hypophysitis has been associated with a number of immunotherapies including Nivolumab, Ipilumumab and other immune checkpoint inhibitors. The timing of the presentation and anterior hypopituitarism is supportive of hypophisitis, although imaging did not show the characteristic changes.

We considered the following possibilities:

1) The coexistence of a pituitary metastasis with radiologically-inapparent hypophysitis

2) Pituitary metastasis which is selectively impairing the hypothalamic signalling to the anterior pituitary whilst sparing the dopaminergic inhibition, the timing with Nivolumab being coincidental

3) Pituitary metastasis with coexistant anterior hypopituitarism due to radiotherapy.