A case report of a patient with Tyr791Phe mutation of the RET proto-oncogene and a unilateral pheochromocytoma without evidence of medullary thyroid carcinoma (MTC) or c-cell hyperplasia : follow-up and best timing for prophylactic thyroidectomy

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 306-326-Neoplasia of Endocrine Tissues: Case Reports
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-324
Maria Mavromati*1, Myriam Amsallem2, Christel Jublanc2, Eric Bruckert2, Laurence Leenhardt3 and Xavier Girerd2
1University Hospital of Geneva, Geneva, Switzerland, 2La Pitié-Salpêtrière Hospital, Paris, France, 3Pitie Salpetriere Hosp, Paris, France
Background : Mutations of the RET-proto-oncogene, which is located on chromosome 10q11.2 and encodes for a membrane tyrosine kinase receptor, are responsible for five different entities (familial MTC, MEN2A, MEN2B, MEN2A with lichen amyloidosis, and Hirschsprung disease)[1]. The Tyr791Phe mutation is believed to be associated with a low penetrance of MTC and the best timing for prophylactic total thyroidectomy needs to be individualized.

 Clinical case: A 27-year woman with an unremarkable medical history presented with a recent history of  severe hypertension, general fatigue, paroxysmal tachycardia, diaphoresis and headaches. Urinary catecholamines and derivates metanephrines showed an elevation of more than 20 times the upper normal limit of 24h-urinary norepinephrine and normetanephrine confirmed twice (norepinephrine : 11 316 nmol/24hrs with N< 590 nmol/24hrs, and normetanephrine : 35 788 nmol/24hrs with N< 2183 nmol/24hrs). Abdominal CT-scan revealed a right adrenal mass of 35 mm diameter and an MRI confirmed the right well-limited adrenal tumor which appeared highly intense in T2-weighted images and hypo-intense in T1-weighted image, progressively and homogenously enhanced after gadolinium injection with more peripheral contrast enhancement. The mass showed no 123-I MIBG uptake, possibly due to necrotic changes whereas a zone of high uptake was found on the left adrenal gland with no evidence of morphologic abnormalities on the CT and MRI-images.

After alpha-adrenergic blocker treatment, a surgical resection of the tumor confirmed the diagnosis of  pheochromocytoma and blood pressure normalized at 3-months after surgery with concomitant normalization of biochemical markers.

Genetic screening revealed a germline Tyr791Phe mutation of the RET proto-oncogene, confirmed twice.

Consequently, the patient was assessed for evidence of MEN2. Basal calcitonin was normal (<5 ng/l) and calcium infusion test was negative (calcitonin < 10 ng/L at – 5, 0, 2, 5, 15 minutes). Thyroid ultrasound examination revealed a 4x6 mm TIRADS 3 nodule with benign cytology. The patient had normal calcium and PTH levels and no clinical stigmata of MEN2.

Total thyroidectomy was suggested but withheld due to the patient’s refusal and a close follow-up was decided.

Conclusion: Tyr791Phe RET mutation is associated with a low penetrance of MTC, however very few cases presenting with pheochromocytoma and no evidence of MTC or C-cell hyperplasia have been described. Best timing for prophylactic thyroidectomy needs to be individualized.

1. Favier, J. and A.-P. Gimenez-Roqueplo, [Genetics of paragangliomas and pheochromocytomas]. Medecine sciences: M/S, 2012. 28(6-7): p. 625-632.

Nothing to Disclose: MM, MA, CJ, EB, LL, XG

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