Questioning the pathogenic role of the pTyr791Phe mutation of the RET proto-oncogene: Insight from a case report.

Unlabelled: The pTyr791Phe mutation of the RET proto-oncogene is associated with a low penetrance of medullar thyroid carcinoma (MTC). Thus, there is a lack in guidelines on management of these patients presenting without a thyroid disease.

Clinical Case: A 27-year-old woman presented with a history of severe hypertension, paroxysmal tachycardia, diaphoresis and headaches. Twenty-four-hour urinary norepinephrine and normetanephrine levels were exclusively up to 20 times the normal limit. CT-scan and MRI found a 35-mm diameter right adrenal tumor, highly intense in T2- and hypo-intense in T1-weighted image, enhanced after gadolinium injection. After alpha-adrenergic blocker treatment, a surgical resection of the tumor was performed; this latter proved to be a pheochromocytoma. Genetic screening only revealed a germline pTyr791Phe mutation of the RET proto-oncogene. However, the patient showed no evidence of MEN2: basal calcitonin was normal and calcium infusion test was negative. Thyroid ultrasound revealed a TIRADS 3 nodule with benign cytology. Total thyroidectomy was suggested but withheld due to the patient's refusal and a close follow-up was decided.

Conclusion: This rare case of pTyr791Phe mutation-related pheochromocytoma without evidence of MTC questions the indication for prophylactic thyroidectomy in mutation carriers, as recent data challenges its pathogenicity.