Endocrine Abstracts

Introduction: Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant multi-glandular tumour syndrome, caused by RET germline mutations.We present a family with three affected generations identified by predictive testing.

Index case and cohort details: A 40-year-old lady referred to ENT clinic with a swelling in the neck. Ultrasound confirmed multinodular goitre with FNAC-THY3. Diagnostic hemithyroidectomy was followed by total thyroidectomy for medullary thyroid cancer (MTC). Genetic testing confirmed heterozygous missense mutation (c.1858T>G, P.Cys620Gly; exon 10 of RET gene).Family history, pedigree charting, and predictive testing identified three affected generations. First generation: mother had chemodectoma and uncle had MTC. Second generation: three out of seven siblings (6F and 1M) of the index case affected (details in table below). Third generation: one offspring has confirmed C-cell hyperplasia following thyroidectomy.

Discussion: The management of this cohort posed complex ethical, diagnostic, and management challenges. As an example with sibling-1, investigations revealed elevated calcitonin, normal urine catecholamines but slightly elevated plasma metanephrines. CT adrenal was normal, but MIBG scan showed increased uptake in the left adrenal. There was non-acceptance of diagnosis and indecisiveness regarding proposed interventions. Following MDT discussion and concerted efforts to engage and prepare the patient, unilateral adrenalectomy was undertaken before thyroidectomy. Plasma metanephrines normalised post adrenalectomy. Subsequently when the date for total thyroidectomy was imminent, an unplanned pregnancy was confirmed. At this point following further extensive discussion of options (in the context of no nodules/cervical lymphadenopathy and calcitonin mildly elevated and stable over 18 months) the patient elected to continue pregnancy with plan for post-partum thyroidectomy.

Conclusion: Our cohort illustrates the challenges posed in managing this rare condition from identifying the mutation, disseminating the diagnosis and communicating management options to affected individuals. Expected behaviour characteristics could vary significantly from that predicated on genotype:phenotype correlations quoted in the literature.