Recurrent ipsilateral pheochromocytoma in carriers of RET p.Cys634 missense mutations.

PURPOSE: The objective of this study was to provide RET genotype-specific data on recurrent ipsilateral pheochromocytoma in multiple endocrine neoplasia type 2A (MEN2A), which are sparse.

METHODS

Kaplan-Meier analyses were performed to determine the risk of recurrent ipsilateral adrenalectomy after subtotal and total adrenalectomy in 221 carriers of RET p.Cys634 missense mutations.

RESULTS

Altogether, pheochromocytoma emerged in 112 of 442 adrenals at risk, for which 63 adrenals underwent total adrenalectomy and 49 adrenals subtotal adrenalectomy. After a mean (median) of 99 (132.9) months, 10 recurrent ipsilateral pheochromocytomas arose in 10 (20.4%) of 49 adrenal remnants. Seven of these 10 adrenal remnants were subjected to total adrenalectomy and 3 to another subtotal adrenalectomy. After 23 and 250 (mean/median 136.5) more months, 2 of the 3 remaining adrenal remnants gave rise to 2 further recurrent ipsilateral pheochromocytomas, which were removed by total adrenalectomy. When the rare publications in which carriers of RET p.Cys634 mutations made up 81-84% of MEN2A patients were combined with the present RET p.Cys634-specific series, the risk of recurrent ipsilateral pheochromocytoma was 6.7% (25 recurrent ipsilateral pheochromocytomas in 375 adrenal remnants), with a mean time interval of 146 months after initial subtotal adrenalectomy.

CONCLUSION

Subtotal adrenalectomy is a viable treatment option for many carriers of RET p.Cys634 mutations who develop an initial pheochromocytoma. Although the adrenal remnant may give rise to recurrent ipsilateral pheochromocytoma after 8-11 years in up to 20% of patients, it is manageable very well in experienced hands, buying the patient valuable time off steroids.