Endocrinol Metab.  2010 Jun;25(2):135-141. 10.3803/EnM.2010.25.2.135.

A Family Presenting with Catastrophic Features due to Pheochromocytoma Associated with Multiple Endocrine Neoplasia 2A

• Lee YJ
• Chon S
• Lee SH
• Lee TW
• Ihm CG
• Noh TJ
• Oh S
• Woo JT
• Kim SW
• Kim JW
• Kim YS

• KMID: 2169020
• DOI: http://doi.org/10.3803/EnM.2010.25.2.135

Abstract

Multiple endocrine neoplasia 2A (MEN 2A) is an autosomal dominant disease that consists of medullary thyroid carcinoma (MTC), pheochromocytoma and parathyroid hyperplasia. The activation of germ-line mutations in the RET proto-oncogene are responsible for MEN 2A. We describe here a rare case of MEN 2A in a patient who presented with an acute catecholamine-induced cardiomyopathy with cardiogenic shock and acute renal failure. The patient was diagnosed with pheochromocytoma and MTC associated with MEN 2A, which was confirmed by the detection of a RET proto-oncogene mutation at exon 11 on codon 634 (Cys634Arg). During familial screening, the patient's younger sister was found to have a benign thyroid nodule. Re-evaluation of this thyroid nodule revealed MTC with the same gene mutation. We also provide a review of the relevant literature.

Keyword

Multiple endocrine neoplasia type 2A; RET proto-oncogene; Pheochromocytoma

MeSH Terms

Acute Kidney Injury
Cardiomyopathies
Codon
Exons
Germ-Line Mutation
Humans
Hyperplasia
Mass Screening
Multiple Endocrine Neoplasia
Multiple Endocrine Neoplasia Type 2a
Pheochromocytoma
Proto-Oncogenes
Shock, Cardiogenic
Siblings
Thyroid Neoplasms
Thyroid Nodule
Codon

Figure

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  Fig. 1 Left adrenal mass. A. Adrenal MRI (T2 weighted image) showed 2.9 × 3.3 × 4.9 cm-sized heterogeneous high signal intensity mass with internal cystic changes in the left adrenal gland. B. 131I-MIBG scan showed increased radioactivity in the left adrenal gland.

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  Fig. 2 Histology of the resected adrenal gland. A. Left adrenal gland specimen, in which a 5 × 4 cm-sized mass was noted. The cut surface showed a rather well-demarcated golden yellow/brown nodular mass with hemorrhage. B. Microscopic finding of pheochromocytoma showed that the area was largely replaced by tumor tissue consisting of clusters or nests or glands of neoplastic cells (H&E stain, × 100, × 400 [in bottom right]).

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  Fig. 3 Histology of the resected thyroid gland. A. Total thyroidectomy specimen was measured to be 9 × 5 cm in size and 25 g in weight. A cut section showed multiple yellow/brown variable-sized nodules. The left thyroid showed a well-defined yellowish mass measuring 1.5 × 1 cm. The right thyroid showed a well-demarcated dark brown mass measuring 2 × 1.5 cm. B. Microscopic finding of medullary thyroid carcinoma showed multiple rather well-defined tumor nodules consisting of nests or clusters of tumor cells with dense fibrous to hyalinized stroma (H&E stain, × 100).

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  Fig. 4 Neck CT of the thyroid nodule in the younger sister of the patient. Diffuse enlargement of the thyroid gland and multiple nodules of various sizes were observed. The largest solid mass was 2.1 cm in size and was found in the left thyroid gland. No abnormal lymph nodes were observed.

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  Fig. 5 Histology of the resected thyroid gland in younger sister of the patient. A. The total thyroidectomy specimen measured 34 g. The left thyroid was 5 × 3 × 3 cm in size, and a cut surface showed multinodular gray/white masses measuring 4 × 3 cm. The right thyroid was 3 × 3 × 2 cm in size, and a cut surface showed a gray/white nodular mass measuring 1.5 × 1 cm. B. Microscopic findings of the thyroid medullary carcinoma showed ill-defined tumor tissue consisting of proliferating round to polygonal cells with granular amphophilic cytoplasm and medium-sized nuclei separated by a vascular stroma, hyalinized collagen, and amyloid tissue arranged in a follicular and trabecular pattern. Associated calcification was evident (H&E stain, × 100).

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  Fig. 6 Direct sequence analysis of exon 11 of the RET gene and the resulting family tree. The analysis shows family members (patient, younger sister of patient) with a mutation at exon 11, codon 634 (C634R), TGC (Cysteine) → CGC (Arginine). A. Wild type, B. Mutant type, C. Pedigree of the patient.

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