Endocrine Abstracts

Introduction: Adrenocortical carcinoma, Pheochromocytomas and Paragangliomas are rare tumors in the general population 1,2, and even more so in association with rare genetic syndromes such as Neurofibromatosis type 1 (NF1)3-6. Current guidelines do not recommend routine screening for these rare and malignant tumors in NF1 patients, posing a risk of missed diagnosis and potentially dangerous outcomes.

Case Presentation: We present a 49-year-old female diagnosed with NF1 at age 10, with a family history of NF1 in her mother. She presented with a subcutaneous thigh lesion that was biopsied and found to be a grade 2 Leiomyosarcoma. Workup with PET-FDG imaging revealed focal uptake in the right adrenal gland and discrete thyroid nodules bilaterally. The patient was asymptomatic, with no history of hypertension, rapid weight gain or weight loss, skin thinning, hyperglycemia, hypertensive spells, palpitations, sweating or panic attacks. Physical examination showed a vitally stable, well-nourished female, with some skin freckling and café au lait lesions, and with no focal signs of hypercortisolism. Further imaging with MRI showed a 3.8 cm right adrenal lesion with intermediate T2 signal enhancement and PETDotatate showed increased uptake of the lesion. Biochemical testing revealed a normal 1mg dexamethasone suppression test, and an elevated urine and plasma metanephrine and normetanephrine levels, more than three times the upper limit of normal. Based on imaging and biochemical testing, a diagnosis of pheochromocytoma was made and the patient was started on doxazosin 10 mg daily with a high-salt diet and underwent laparo No table of contents entries found. scopic right adrenalectomy without complication. Pathology confirmed a 4.1 cm malignant pheochromocytoma with capsular invasion. Evaluation of the thyroid nodules with fineneedle aspiration is pending.

Discussion: The patient had a silent clinical presentation, and imaging results were suggestive of an adrenocortical carcinoma. However, biochemical tests revealed a different diagnosis, which was further confirmed by pathology as malignant pheochromocytoma. Although adrenal pathologies are rare in patients with NF1, they are well documented and can lead to devastating outcomes if missed3-6. Current guidelines do not recommend routine screening for adrenal pathologies in patients with NF1. In our case, the diagnosis may have been overlooked if not for the incidental finding of leiomyosarcoma, which prompted further imaging and biochemical testing. While the patient’s surgical course was uneventful, the same may not be true for all NF1 patients with undiagnosed pheochromocytomas. We recommend reviewing the guidelines on screening for adrenal tumors in all NF1 patients planning to undergo surgery and/or conception, to mitigate the risk of a pheochromocytoma crisis.

References:
1. Kebebew E, Reiff E, Duh QY, Clark OH, McMillan A. Extent of disease at presentation and outcome for adrenocortical carcinoma: have we made progress? World J Surg. 2006 May;30(5):872-8. doi: 10.1007/s00268-005-0329-x.
2. Beard CM, Sheps SG, Kurland LT, Carney JA, Lie JT. Occurrence of pheochromocytoma in Rochester, Minnesota, 1950 through 1979. Mayo Clin Proc. 1983 Dec;58(12):802-4.
3. Menon RK, Ferrau F, Kurzawinski TR, Rumsby G, Freeman A, Amin Z, Korbonits M, Chung TT. Adrenal cancer in neurofibromatosis type 1: case report and DNA analysis. Endocrinol Diabetes Metab Case Rep. 2014;2014:140074. doi: 10.1530/EDM-14-0074.
4. Kollurage UA, Jayawikrama RS, Yasawardana AD, Atapattu N. Adrenal crisis in metastatic adrenal cortical carcinoma in an infant with neurofibromatosis type 1. Sri Lanka J Child Health. 2019;48:74–6.
5. Najafi-Semnani M, Rajabi-Moghaddam M, Abbaszadeh H. Adrenocortical carcinoma in a patient with neurofibromatosis type 1: A case report. Caspian J Intern Med. 2021 Fall;12(4):613-617. doi: 10.22088/cjim.12.4.613.
6. Gruber LM, Erickson D, Babovic-Vuksanovic D, Thompson GB, Young WF Jr, Bancos I. Pheochromocytoma and paraganglioma in patients with neurofibromatosis type 1. Clin Endocrinol (Oxf). 2017 Jan;86(1):141-149. doi: 10.1111/cen.13163.