MON-415 Pituitary Carcinoma With Sequential Hormone Hypersecretion And A Novel Renal Complication Of Hormone Excess

Background: Pituitary carcinoma is a rare diagnosis, occurring in <1% of pituitary tumours. Most are hormonally active and resistant to conventional treatment. We present a rare case of a malignant lactotroph tumour whose extreme and evolving secretory phenotype has induced an unprecedented form of nephropathy. Case: A 55 year old man presented to ophthalmology with painful right third nerve palsy. Subsequent imaging revealed a 24 x 26 mm sellar mass extending into the right cavernous sinus and encroaching upon the optic chiasm. Endocrine evaluation demonstrated prolactin (PRL) of 68,000 mIU/L and accompanying hypogonadism (testosterone 1.3 nmol/L, FSH 1.8 IU/L, LH 1.4 IU/L), hypoadrenalism (peak cortisol 272 nmol/L after 250 mcg synacthen) and hypothyroidism (TSH 2.9 mIU/L, T4 8 pmol/L). IGF1-1 was also at the lower end of the reference range (10 nmol/L). He made an initial good response to cabergoline with PRL falling to 1570 mIU/L, resolution of visual symptoms, tumour shrinkage to 7 x 16 mm and restoration of HPA axis function. Five years later he demonstrated escape from hormone control with PRL rising to 32,000 mIU/L and return of the ophthalmoplegia, despite escalation of cabergoline to 3.5mg weekly. Unexpectedly, he also developed acute ketotic diabetes mellitus secondary to new onset acromegaly (GH >100 ug/L, IGF-1 97 nmol/L). The tumour remnant had expanded into the cavernous sinus on MRI. Biopsy of the lesion showed a tumour with strong PRL staining, micro-vacuolation, sparse GH staining and Ki-67 of 15-20% suggesting an aggressive nature and potentially in keeping with the rare acidophilic stem cell tumour subtype. He underwent stereotactic pituitary radiotherapy and later commenced pegvisomant therapy after a failed octreotide trial. Following this, prolactin levels continued to rise. Unfortunately, subsequent investigations for back pain with bilateral hand paraesthesia (at first considered secondary to acromegaly) revealed metastatic lesions in spine, lung and stomach - the latter confirmed to be of PRL-secreting neuroendocrine origin on biopsy. There was no uptake on octreotide scan. In response to new renal dysfunction (creatinine 463 umol/L with microscopic haematuria and proteinuria), a renal biopsy was also performed and revealed changes compatible with interstitial nephritis with cast nephropathy. The tubular casts stained positive for PRL, and serum PRL at this time reached a peak of 3.7 million mIU/L. Temolozamide has been commenced, and the patient may later be considered for immunotherapy . Conclusion: This is the first documented case of prolactin cast nephropathy and a rare example of a changing tumour secretion pattern, with intractable acute on chronic hyperprolactinaemia and acute acromegaly, in a case of metastatic pituitary carcinoma.