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

Andreas Machens1, Kerstin Lorenz2, Frank Weber3

  • 1Medical Faculty, Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, D-06097, Halle (Saale), Germany. AndreasMachens@aol.com.

Endocrine
|May 17, 2022
PubMed
Abstract

Insights

Subtotal adrenalectomy is a viable option for Multiple Endocrine Neoplasia type 2A (MEN2A) patients with RET p.Cys634 mutations. Recurrent pheochromocytoma can occur in up to 20% of patients but is manageable.

Area of Science:

  • Endocrinology
  • Oncology
  • Genetics

Background:

  • Multiple Endocrine Neoplasia type 2A (MEN2A) is a hereditary condition often associated with pheochromocytoma.
  • RET proto-oncogene mutations, particularly p.Cys634 missense mutations, are common in MEN2A and linked to pheochromocytoma development.
  • Data on recurrent ipsilateral pheochromocytoma after adrenalectomy in specific RET genotypes are limited.

Purpose of the Study:

  • To provide RET genotype-specific data on recurrent ipsilateral pheochromocytoma in MEN2A.
  • To analyze the risk of pheochromocytoma recurrence after subtotal versus total adrenalectomy in carriers of RET p.Cys634 mutations.

Main Methods:

  • Kaplan-Meier survival analyses were used to assess recurrence risk.
  • The study included 221 carriers of RET p.Cys634 mutations.
  • Data were combined with previously published series focusing on RET p.Cys634 mutations.

Main Results:

  • Pheochromocytoma occurred in 112 of 442 at-risk adrenal glands.
  • Recurrent ipsilateral pheochromocytoma arose in 20.4% (10 of 49) of adrenal remnants after subtotal adrenalectomy, with a mean follow-up of 132.9 months.
  • Pooled analysis with literature data indicated a 6.7% risk of recurrent ipsilateral pheochromocytoma after initial subtotal adrenalectomy, with a mean interval of 146 months.

Conclusions:

  • Subtotal adrenalectomy is a feasible treatment for initial pheochromocytoma in RET p.Cys634 mutation carriers.
  • While recurrent ipsilateral pheochromocytoma can occur in up to 20% of patients after 8-11 years, it is manageable in experienced centers.
  • This approach allows patients valuable time off steroid replacement therapy.
Keywords:
Adrenal RemnantIpsilateral RecurrenceMultiple Endocrine Neoplasia 2APheochromocytomaRET Proto-OncogeneSubtotal Adrenalectomy

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