Endocrine Abstracts

Introduction: Neurofibromatosis type 1 (NF-1) (1/3000 live births) is a rare genetic cause for hereditary pheochromocytoma (0.1-5.7%) with unclear incidence and risk of malignancy. There is no current UK screening program for patients with NF-1 for pheochromocytoma/paraganglioma.

Methods: A retrospective review of patients who were diagnosed with pheochromocytoma in the context of NF-1 following referral to the adrenal multidisciplinary team at Oxford.

Results: 13 patients with adrenal abnormalities in the context of NF1 were identified (2001-2024), 7/13 females, average age at date of surgery 51 years, range 29-70 years. 11 patients had histologically proven pheochromocytoma. Most patients were diagnosed incidentally on scans performed for an unrelated condition (7/8). Details available from the time of presentation show: only 1 patient presented with hypertensive symptoms, several were shown to be hypertensive on testing after the adrenal lesion was identified, 5 had significantly elevated plasma metanephrines (PMT) (normetanephrines 10,000 to >25,000 pmol/L) and 2 had significantly elevated urine normetadrenaline levels, 8/12 had tumour size ≥ 5cm, and 2/11 had metastatic disease (liver, lymph nodes) at presentation. 5/6 had a PASS score ≥4. Regarding outcomes, 12 surgical resections on 11 patients were performed; laparoscopic adrenalectomy n = 9, open adrenalectomy n = 3. 1 patient required 2 operations for bilateral disease. 2 patients had metastatic disease requiring further treatments (1 patient had debulking of recurrent disease followed by MIBG therapy, the second received MIBG therapy). Three patients have died. Of the other 2 patients, one had an adrenal abnormality radiologically in keeping with adrenal myelolipoma (normal PMT), one had a small nodule with mild PMT and is under observation.

Conclusions: Significant risk of large tumours and malignancy potential was observed with pheochromocytoma associated with NF-1. The majority were asymptomatic, but would have been identified with biochemical testing, raising the question about the potential need for a structured screening pathway to identify pheochromocytoma early among patients with NF-1 to enable timely intervention to prevent potential metastatic disease. Our case series highlights the need for larger studies (potential with a national registry) to identify risk factors for more aggressive disease and the need for greater screening for NF1 patients.