10 research outputs found
Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance
Peer reviewe
Cumulative Risk Impact of Five Genetic Variants Associated with Papillary Thyroid Carcinoma
Correction: Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance
Correction: Ultra-Rare Mutation in Long-Range Enhancer Predisposes to Thyroid Carcinoma with High Penetrance
The penetrance of MEN2 pheochromocytoma is not only determined by RET mutations
Multiple endocrine neoplasia type 2 (MEN2) is a rare syndrome subdivided into 2 main entities: MEN2A and MEN2B (Donis-Keller et al. 1993, Mulligan et al. 1993, Eng et al. 1996). Genetic results can predict the natural history of medullary thyroid carcinoma (MTC) depending on the mutation of RET. This is the basis for ATA guidelines giving different ages to perform early thyroidectomy in such patients (Wells et al. 2015). MEN2A and MEN2B are also characterized by the occurrence of pheochromocytoma (PHEO), though less frequent than MTC. PHEO is a chromaffin tumor arising from the medullar zone of the adrenals and responsible for mortality if left undiagnosed (Lenders et al. 2005). Precise comparative large-scale epidemiological data on PHEO penetrance in different geographical zones are however missing in the literature as the majority of published studies were coming from a single Center or a single country
Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2:an international retrospective population-based study
Background The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2.Methods This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients' RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy.Findings 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent.Interpretation The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.</p
Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study
Background The prevention of medullary thyroid cancer in patients with
multiple endocrine neoplasia type 2 syndrome has demonstrated the
ability of molecular diagnosis and prophylactic surgery to improve
patient outcomes. However, the other major neoplasia associated with
multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well
characterised in terms of occurrence and treatment outcomes. In this
study, we aimed to systematically characterise the outcomes of
management of phaeochromocytoma associated with multiple endocrine
neoplasia type 2.
Methods This multinational observational retrospective population-based
study compiled data on patients with multiple endocrine neoplasia type 2
from 30 academic medical centres across Europe, the Americas, and Asia.
Patients were included if they were carriers of germline pathogenic
mutations of the RET gene, or were first-degree relatives with
histologically proven medullary thyroid cancer and phaeochromocytoma. We
gathered clinical information about patients’ RET genotype, type of
treatment for phaeochromocytoma (ie, unilateral or bilateral operations
as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic
operations), and postoperative outcomes (adrenal function, malignancy,
and death). The type of surgery was decided by each investigator and the
timing of surgery was patient driven. The primary aim of our analysis
was to compare disease-free survival after either adrenal-sparing
surgery or adrenalectomy.
Findings 1210 patients with multiple endocrine neoplasia type 2 were
included in our database, 563 of whom had phaeochromocytoma. Treatment
was adrenalectomy in 438 (79%) of 552 operated patients, and
adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence
occurred in four (3%) of 153 of the operated glands after
adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717
glands operated by adrenalectomy (p=0.57). Postoperative adrenal
insufficiency or steroid dependency developed in 292 (86%) of 339
patients with bilateral phaeochromocytoma who underwent surgery.
However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who
underwent adrenal-sparing surgery did not become steroid dependent.
Interpretation The treatment of multiple endocrine neoplasia type
2-related phaeochromocytoma continues to rely on adrenalectomies with
their associated Addisonian-like complications and consequent lifelong
dependency on steroids. Adrenal-sparing surgery, a highly successful
treatment option in experienced centres, should be the surgical approach
of choice to reduce these complications