Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal dominant neuroendocrine neoplasia syndrome characterised by early onset medullary thyroid carcinoma (MTC) in all patients, phaeochromocytoma and multiple extra-endocrine features. We present a case of late diagnosis of MEN2B illustrating the challenge of early diagnosis.

Case report: A 12 year old boy presented after lifetime of investigation. There was no relevant family history. He had atypical left talipes equinovarus caused by a tethered spinal cord which was surgically released, swallowing difficulties, gastroesophageal reflux, constipation, left duplex kidney with grade 3 reflux, tracheomalacia, amblyopia, speech and language delay, articulatory difficulties, asthma and allergic rhinitis. At the age of 4, genetic investigation revealed normal karyotype, MLPA, and array CGH. At 10 he was enrolled into the pilot 100,000 genome project and about 2000 genes were analysed. This revealed a single pathogenic variant: a heterozygous missense pathogenic RET variant, c.2753T>C p.(Met 918Thr) diagnostic of MEN2B. Examination revealed marfanoid habitus with arm span exceeding height, hyperflexibility, prognathism, enlarged tongue with mucosal neuromas, high arched palate, full lips, eversion of upper lids and unremarkable thyroid examination but enlarged cervical lymph nodes. Biochemical measurements showed a Calcitonin level 7000 ng/l [0–12.7], CEA 28.7 μg/l [0–3.4] and normal plasma metanephrines. Thyroid ultrasonography revealed bilateral medullary thyroid nodules with local nodal involvement and chest CT showed bilateral lung nodules. The patient had total thyroidectomy with modified radical neck dissection, the cancer had also infiltrated the right recurrent laryngeal nerve. Pathology confirmed the presence of bilateral medullary thyroid cancer and involvement of 55/137 excised lymph nodes. Calcitonin levels decreased to 5010 ng/l. Postoperatively he had stridor from vocal cord paresis. He is currently well, no chemotherapy is planned presently.

Conclusion: MEN2B is a rare disease consisting of a de novo mutation in 90% of patients. Also, MTC may be asymptomatic until advanced stage of disease. However, different extra-endocrine features will be present in 100% of patients and awareness of these is essential for early diagnosis and improved outcome.