Advances in risk-oriented surgery for multiple endocrine neoplasia type 2

Abstract

Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia type 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time provided by early identification of asymptomatic MEN2 carriers under biochemical surveillance delimits a 'window of opportunity', within which (i) pre-emptive total thyroidectomy alone is adequate, circumventing morbidity attendant to central node dissection; (ii) subtotal 'tissue-sparing' adrenalectomy is sufficient, trading the risk of steroid dependency for the risk of a second pheochromocytoma in the adrenal remnant and (iii) parathyroidectomy is limited to enlarged glands, trading the risk of postoperative hypoparathyroidism for the risk of leaving behind hyperactive parathyroid glands. Future research should delineate further the mutation-specific, age-dependent penetrance of pheochromocytoma and primary hyperparathyroidism to refine the risk-oriented approach to MEN2. The sweeping changes in the management of MEN2 since the new millenium hold the hope that death and major morbidity from this uncommon disease can be eliminated in our lifetime.

Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations

“…Table depicts the demographic genetic, and histopathological characteristics of all 167 children who underwent prophylactic thyroidectomy, stratified by the presence or absence of central node dissection. Children had concomitant central node dissection more often in the earlier years of the study (median operative year 2003 versus 2007; P < 0·001), reflecting the state of knowledge at the time. Likewise, these children tended to be slightly older at prophylactic thyroidectomy (median age 7 versus 5 years; P = 0·015) and more often to have occult MTC (41 versus 23·9 per cent; P = 0·022), even though statistical significance was lost for these associations after correction for multiple testing ( Table ).…”

“…Informed consent was obtained from all patients and/or their legal guardians before the operation, in line with standard practice of care according to the practice guidelines of the German Society of Surgery. Node dissection was performed more often in the beginning because initial genetic association studies seemingly implied more rapid progression of MTC. In line with the 2015 revised American Thyroid Association (ATA) practice guidelines for the management of MTC, the term prophylactic thyroidectomy is used here to define removal of the thyroid before MTC develops or while it is clinically inapparent and confined to the gland.…”

A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma

“…That is when the serum calcitonin level is elevated, but before the occurrence of metastasis. Thus, biochemical cure can be achieved(250,251,271). First screening of RET gene mutation should be performed at less than one year of age for patients in highest-risk group, one to five years for high-risk group and five years for moderate-risk group(98,250).…”

Flush after unilateral adrenalectomy

“…Skin lesions in MEN2A syndrome (a part from cutaneous manifestations of high blood pressure crisis and pheocromocytoma) involves lichen amyloidosis in some cases (not this one) (23). Nowadays a refine of risk-oriented management of persons with MEN2A syndrome is registered (24).…”