Natural history, treatment, and long-term follow up of patients with multiple endocrine neoplasia type 2B: an international, multicentre, retrospective study.

BACKGROUND: Multiple endocrine neoplasia type 2B is a rare syndrome caused mainly by Met918Thr germline RET mutation, and characterised by medullary thyroid carcinoma, phaeochromocytoma, and extra-endocrine features. Data are scarce on the natural history of multiple endocrine neoplasia type 2B. We aimed to advance understanding of the phenotype and natural history of multiple endocrine neoplasia type 2B, to increase awareness and improve detection. METHODS: This study was a retrospective, multicentre, international study in patients carrying the Met918Thr RET variant with no age restrictions. The study was done with registry data from 48 centres globally. Data from patients followed-up from 1970 to 2016 were retrieved from May 1, 2016, to May 31, 2018. Our primary objectives were to determine overall survival, and medullary thyroid carcinoma-specific survival based on whether the patient had undergone early thyroidectomy before the age of 1 year. We also assessed remission of medullary thyroid carcinoma, incidence and treatment of phaeochromocytoma, and the penetrance of extra-endocrine features. FINDINGS: 345 patients were included, of whom 338 (98%) had a thyroidectomy. 71 patients (21%) of the total cohort died at a median age of 25 years (range <1-59). Thyroidectomy was done before the age of 1 year in 20 patients, which led to long-term remission (ie, undetectable calcitonin level) in 15 (83%) of 18 individuals (2 patients died of causes unrelated to medullary thyroid carcinoma). Medullary thyroid carcinoma-specific survival curves did not show any significant difference between patients who had thyroidectomy before or after 1 year (comparison of survival curves by log-rank test: p=0·2; hazard ratio 0·35; 95% CI 0.07-1.74). However, there was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). There was a significant difference in remission status between patients who underwent thyroidectomy before and after the age of 1 year (p<0·0001). In the other 318 patients who underwent thyroidectomy after 1 year of age, biochemical and structural remission was obtained in 47 (15%) of 318 individuals. Bilateral phaeochromocytoma was diagnosed in 156 (50%) of 313 patients by 28 years of age. Adrenal-sparing surgery was done in 31 patients: three (10%) of 31 patients had long-term recurrence, while normal adrenal function was obtained in 16 (62%) patients. All patients with available data (n=287) had at least one extra-endocrine feature, including 106 (56%) of 190 patients showing marfanoid body habitus, mucosal neuromas, and gastrointestinal signs. INTERPRETATION: Thyroidectomy done at no later than 1 year of age is associated with a high probability of cure. The reality is that the majority of children with the syndrome will be diagnosed after this recommended age. Adrenal-sparing surgery is feasible in multiple endocrine neoplasia type 2B and affords a good chance for normal adrenal function. To improve the prognosis of such patients, it is imperative that every health-care provider be aware of the extra-endocrine signs and the natural history of this rare syndrome. The implications of this research include increasing awareness of the extra-endocrine symptoms and also recommendations for thyroidectomy before the age of 1 year. FUNDING: None

Chemical neuroanatomy of the hypothalamo-hypophyseal system in sturgeons

International audienceThe preoptic-hypothalamo-hypophyseal system of sturgeons, located at the base of the brain, has a neurosecretory role exerted by hypophysiotropic neurons most of them located in the preoptic and hypothalamic periventricular region. The majority of those cells are of the cerebrospinal fluid-contacting type and exhibit short processes reaching the ventricular lumen. Moreover, the processes of those hypophysiotropic neurons course along the hypothalamic floor toward the hypophysis forming a preoptic-hypothalamo-hypophyseal tract. This chapter summarizes available data on the distribution of several hypophysiotropic factors, such as galanin, neurophysin, somatostatin, or gonadotropin-releasing hormone, in the preoptic-hypothalamo-hypophyseal system of sturgeons obtained by the use of immunohistochemical techniques. Immunoreactive neurons to those substances were found in the preoptic and hypothalamic nuclei, and immunoreactive fibers were observed along the preoptic-hypothalamo-hypophyseal tract and in the hypophysis, indicating their hypophysiotrophic role in the brain of sturgeons. Thus, most of the neuropeptides and neurohormones found in tetrapods are also present in sturgeons, suggesting that their common ancestors already possessed such regulatory systems. Unfortunately, because of the difficulty in approaching the physiology of sturgeons (size, cost, etc.), the number of experimental studies aiming at deciphering the roles of such neuropeptides and neurohormones is very limited, although we can speculate that part of the functions supported by these neurohormones would be similar. © Springer International Publishing AG, part of Springer Nature 2018. All rights reserved