Beyond MTC: Clinical Manifestations of MEN2A in Hereditary Medullary Thyroid Cancer Patients in a Tertiary Centre
https://doi.org/10.15605/jafes.041.S1
- Author:
Qin Zhi Lee
1
;
Chin Voon Tong
1
;
Raja Nurazni Raja Azwan
1
;
Zanariah Hussein
1
Author Information
1. Endocrinology Unit, Department of Medicine, Hospital Putrajaya
- Publication Type:Journal Article
- MeSH:
Humans;
Multiple Endocrine Neoplasia Type 2a;
Thyroid Neoplasms
- From:
Journal of the ASEAN Federation of Endocrine Societies
2026;41(S1):80-
- CountryPhilippines
- Language:English
-
Abstract:
Introduction:Medullary thyroid carcinoma (MTC) has the highest
familial predisposition syndrome of any hereditary cancer
syndrome. The most common subtype of hereditary MTC
is multiple endocrine neoplasia type 2A (MEN2A), which is
an autosomal dominant syndrome characterized by MTC,
pheochromocytoma, and primary hyperparathyroidism
(HPP). This study evaluates the genotypic distribution,
phenotypic manifestations, and clinical characteristics of
MEN2A within a retrospective MTC cohort.
Methodology:A retrospective audit of MTC patients was conducted at
a tertiary centre. Patients with clinically or genetically
confirmed hereditary MTC were identified for further
analysis. Electronic medical records were reviewed for
demographic data, RET germline mutations, occurrence
of pheochromocytoma and HPP, laterality of disease, and
documented surgical interventions.
Results:In all, 18 patients (31.6%) were classified as hereditary from
a cohort of 57 patients with a median age at diagnosis of 29.2
years. Among genetically confirmed cases with available
variant data (n = 11), mutations predominantly involved
exon 11 codon 634 (90.9%, n = 10), including p.Cys634Arg
(n = 4), p.Cys634Tyr, and p.Cys634Ser, with one codon 618
mutation.
Extrathyroidal manifestations were common. Pheochromocytoma occurred in 50.0% (n = 9), of which 77.8% (n = 7)
were bilateral. Most patients underwent adrenalectomy,
including bilateral procedures in those with bilateral
disease. HPP was identified in 44.4% (n = 8), managed with
selective parathyroidectomy. Both pheochromocytoma
and HPP were present in 22.2% (n = 4), while isolated MTC
occurred in 27.8% (n = 5).
Conclusion:Hereditary MTC in our cohort is predominantly associated
with high-risk codon 634 RET mutations and demonstrates
substantial penetrance of pheochromocytoma and HPP.
The high frequency of bilateral adrenal involvement
highlights the importance of systematic biochemical
surveillance and appropriately timed surgical management
in MEN2A. A nationwide registry would be timely.
- Full text:2026080413425594212EP_A110.pdf
