Largest study to date shows early surgery vital in multiple endocrine neoplasia type 2B

medwireNews: A multicentre collaborative study shows that early thyroidectomy offers a high chance of a cure for patients with multiple endocrine neoplasia type 2B, as long as it is performed before the age of 1 year.

However, “[t]he reality is that the majority of children with the syndrome will be diagnosed after this recommended age”, write Frederic Castinetti (La Conception Hospital, Marseille, France) and co-researchers in The Lancet Diabetes & Endocrinology.

In a linked commentary, Maya Lodish (University of California, San Francisco, USA) stresses: “If more clinicians recognised the presenting symptoms of gastrointestinal dysmotility and absence of tears in infancy as potentially associated with multiple endocrine neoplasia type 2B, more children could undergo age-appropriate thyroidectomy, which has been shown to improve survival in hereditary medullary thyroid cancer.”

In this cohort of 345 patients, just 20 were operated on before they reached 1 year of age. But all patients had at least one non-endocrine symptom of multiple endocrine neoplasia type 2B, most commonly ganglioneuromatosis (97%), marfanoid habitus (73%) and pseudo Hirschsprung’s disease or severe constipation (65%).

Two of the patients who underwent surgery before the age of 1 year died of causes other than medullary thyroid carcinoma and 15 (83%) of the remaining 18 patients had no biochemical or imaging evidence of carcinoma at a median of 5.2 years after surgery.

By contrast, at a median of 13 years after thyroidectomy, just 15% of the 318 patients who were older (median 14 years) at the time of surgery were in remission, with 65% having persistent disease and 33% having metastatic disease. A further 64 (20.1%) patients died, with 43 (13.5%) deaths due to medullary thyroid carcinoma.

There were no data for 59 patients and seven did not undergo surgery, mostly because they had metastatic and progressive disease at the time of diagnosis.

The researchers note that there have “been suggestions to postpone thyroidectomy to the age of 4 years”. However, in this study, nine (56%) of the 16 patients who underwent surgery between the ages of 1 and 4 years had persistent disease, which the team says “calls for caution”.

Lodish observes that “referral to an experienced surgeon is crucial as paediatric thyroid cancer patients referred to high-volume facilities have improved outcomes.”

The other major consequence of multiple endocrine neoplasia type 2B is phaeochromocytoma. This occurred in 49% of 313 patients with data on this outcome, by a median of 24 years of age.

Of note, the study shows good outcomes for patients who underwent adrenal-sparing surgery for phaeochromocytoma. Twenty-six patients who required bilateral surgery underwent at least one adrenal-sparing surgery, and 62% of these retained normal adrenocortical function, compared with none of the 69 patients who underwent total adrenalectomy.

Lodish notes that adrenal-sparing surgery outcomes have not previously been reported in this population. She points out that 52% of patients in this study had bilateral phaeochromocytoma, “highlighting the need to consider adrenal-sparing surgery to avoid the outcome of functional adrenal insufficiency.”

By Eleanor McDermid

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(18)30336-X
Lancet Diabetes Endocrinol 2019; doi:10.1016/S2213-8587(18)30353-X
Martin Savage
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