Pheochromocytoma and primary hyperparathyroidism: a very rare association in a neurofibromatosis type 1 patient unmasked by Takotsubo syndrome.

SUMMARY: Neurofibromatosis type 1 is an autosomal dominant disease characterized by cutaneous, bone, and neurocognitive manifestations and an increased risk of neoplasms - more frequently cutaneous neurofibromas and optic gliomas and more rarely pheochromocytomas/paragangliomas, solitary parathyroid adenomas with primary hyperparathyroidism, and breast carcinomas. We present a case of a 48-year-old woman with an unexpected presentation of Takotsubo syndrome that culminated in a synchronous diagnosis of pheochromocytoma, primary hyperparathyroidism, and invasive breast carcinoma (pN2(R0)N1) in the context of previously unknown neurofibromatosis type 1. The patient underwent simultaneous right adrenalectomy and lower parathyroidectomy nearly one month after left lumpectomy with axillary ganglion dissection. No complications were reported after adequate alpha- and beta-adrenergic blockade before or during both surgical interventions. Furthermore, after definitive treatment of catecholamine hypersecretion, postoperative chemoradiotherapy was required. Our case highlights the importance of differential diagnosis with multiple endocrine neoplasia type 2 and the relevance of multidisciplinary teams in the management of complications associated with neurofibromatosis type 1, namely those related to neoplasms.

LEARNING POINTS: Neurofibromatosis type 1 (NF1) is an autosomal dominant disease characterized by cutaneous, bone, and neurocognitive manifestations and an increased risk of neoplasms, namely pheochromocytomas/paragangliomas, solitary parathyroid adenomas, and breast carcinomas. Pheochromocytomas/paragangliomas (PPGLs) occur in up to 15% of patients. Pheochromocytomas can rarely present as Takotsubo syndrome (TS), and the occurrence of TS in NF1 patients is even rarer. In addition, the co-occurrence of PPGLs and primary hyperparathyroidism (PHPT) in NF1 is very infrequent, mimicking MEN 2A syndrome. This is the first case described in the literature of a patient with NF1 and a synchronous diagnosis of pheochromocytoma, PHPT, and breast carcinoma, highlighting the relevance of a high level of suspicion of all the nosological entities that can be associated with NF1 in order to allow an early diagnosis.