This article is more than 5 years old. Information may no longer be current.
Early thyroidectomy can improve survival in multiple endocrine neoplasia type 2B
Click Here to Manage Email Alerts
Among children with multiple endocrine neoplasia type 2B, thyroidectomy before age 1 year can improve chances of survival into adulthood, whereas adrenal-sparing surgery can improve functional outcomes, according to an analysis of global registry data published in The Lancet Diabetes & Endocrinology.
“Multiple endocrine neoplasia type 2B is a rare, genetic syndrome including medullary thyroid carcinoma in 100% of cases, inconstant pheochromocytoma and extra-endocrine signs,” Frederic Castinetti, MD, PhD, associate professor of endocrinology at Aix-Marseille University, France, told Endocrine Today. “Despite the fact that management should only be performed by expert centers, all physicians should be aware of the signs leading to a diagnosis of multiple endocrine neoplasia type 2B, as the chance of remission increases when the thyroidectomy is performed at the earliest possible age. International guidelines recommend thyroidectomy before the age of 1 year, and our results are in accordance with these recommendations.”
In a retrospective study, Castinetti and colleagues analyzed data from 345 patients with multiple endocrine neoplasia type 2B carrying the Met918Thr RET variant, with no age restrictions, using registry data from 48 centers globally (184 women). Primary objectives included determining overall survival, as well as medullary thyroid carcinoma-specific survival, based on whether the patients had undergone early thyroidectomy before age 1 year. Researchers also assessed the remission rate of medullary thyroid carcinoma, incidence and treatment of pheochromocytoma and extra-endocrine features.
Within the cohort, 338 patients had a thyroidectomy, with 20 patients undergoing the procedure before age 1 year (median age, 9 months). Researchers observed 327 cases of medullary thyroid carcinoma (median age of thyroidectomy, 14 years). It was limited to the thyroid in only 53 (17%) patients who underwent lymph node dissection.
The researchers observed a difference in remission status between patients who underwent thyroidectomy before and after age 1 year (P < .001). At a median of 5.2 years after thyroidectomy, 15 of 18 surviving patients who underwent thyroidectomy before age 1 year were in biochemical or structural remission, according to researchers. In the group of patients who had thyroidectomy after age 1 year, 64 patients (20%) had died, including 43 due to medullary thyroid carcinoma (median age, 25 years). At last follow-up at a median of 13 years after thyroidectomy, 47 patients (15%) were in biochemical or structural remission, and 207 patients (65%) had persistent disease, including 104 (33%) who progressed to systemic metastases requiring chemotherapy (n = 8), oral targeted therapy (n = 34) or liver-directed radiofrequency ablation (n = 2).
Researchers observed 153 patients (49%) with a diagnosis of at least one pheochromocytoma (median age, 24 years). Among these patients, 31 had at least one adrenal-sparing surgery. Among all patients who underwent surgery, 14 developed recurrence (median age, 34 years), including three patients who had undergone adrenal-sparing surgery and 11 who had an adrenalectomy.
The researchers noted that all patients with available data (n = 287) had at least one extra-endocrine feature, including marfanoid body habitus, ganglioneuromas or gastrointestinal signs, with surgical intervention necessary in 28 patients.
“The different clinical courses and outcomes of medullary thyroid carcinoma and pheochromocytoma, in addition to the varying penetrance of extra-endocrine features, make multiple endocrine neoplasia type 2B a complex syndrome characterized by wide phenotypic variability despite being defined a single-gene disorder,” the researchers wrote.
“Early thyroidectomy is mandatory in multiple endocrine neoplasia type 2B, as shown by a significant difference in the rate of remission between patients operated on before age 1 year and those who underwent thyroidectomy after age 1 year. Of note, there is a group of patients who are cured, despite delayed thyroidectomy.”
Castinetti noted that pheochromocytoma appear in the majority of the patients at a young age, and adrenal sparing surgery can allow for normal function in up to two-thirds of patients.
In commentary accompanying the study, Maya B. Lodish, MD, a pediatric endocrinologist in the department of pediatric endocrinology at the University of California, San Francisco, wrote that the study provides crucial insights into extra-endocrine features of the condition and provides data for outcomes of current investigations including adrenalectomy and thyroidectomy.
The study also highlights the importance of early diagnosis, she wrote, showing a significant difference in remission status between patients operated on before vs. after age 1 year.
“The current study improves our understanding of the natural history of multiple endocrine neoplasia type 2B, which is invaluable as a baseline comparison,” Lodish wrote. “It remains to be addressed whether RET-specific inhibitors will affect clinical outcomes in patients with this rare syndrome, a question which will require years of follow-up.” – by Regina Schaffer
For more information:
Frederic Castinetti, MD, PhD, can be reached at Aix-Marseille University, Department of Endocrinology, Jardin du Pharo, 58 Boulevard Charles Livon, 13007 Marseille, France; email: frederic.castinetti@ap-hm.fr.
Disclosures: The authors and Lodish report no relevant financial disclosures.
Click Here to Manage Email Alerts