TY - JOUR
T1 - Understanding the clinical course of genotype-negative MEN1 patients can inform management strategies
AU - Pieterman, Carolina R.C.
AU - Hyde, Samuel M.
AU - Wu, Si Yuan
AU - Landry, Jace P.
AU - Chiang, Yi Ju
AU - Christakis, Ioannis
AU - Grubbs, Elizabeth G.
AU - Fisher, Sarah B.
AU - Graham, Paul H.
AU - Waguespack, Steven G.
AU - Perrier, Nancy D.
N1 - Funding Information:
JPL was supported by the National Institutes of Health under award number T32 CA 009599. The MEN1 research genetic testing was supported by the National Institutes of Health/National Cancer Institute under award number P30 CA016672.
Funding Information:
JPL was supported by the National Institutes of Health under award number T32 CA 009599 . The MEN1 research genetic testing was supported by the National Institutes of Health/National Cancer Institute under award number P30 CA016672.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2021/1
Y1 - 2021/1
N2 - Background: It is unclear whether genotype-negative clinical multiple endocrine neoplasia type 1 patients derive equal benefit from prospective surveillance as genotype-positive patients. Methods: In this retrospective cohort study, we compared genotype-negative patients with clinical multiple endocrine neoplasia type 1 with genotype-positive index cases. Primary outcome was age-related penetrance of manifestations; secondary outcomes were disease-specific survival and clinical course of endocrine tumors. Results: We included 39 genotype-negative patients with clinical multiple endocrine neoplasia type 1 (Male: 33%) and 63 genotype-positive multiple endocrine neoplasia type 1 index cases (Male: 59%). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were 65 years old at last follow-up; genotype-positive multiple endocrine neoplasia type 1 index cases were 50 (P <.001). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were significantly older at their first and second primary manifestation. Only 1 developed a third primary manifestation. No genotype-negative patients with clinical multiple endocrine neoplasia type 1 with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumor. Disease-specific survival was significantly better in genotype-negative patients with clinical multiple endocrine neoplasia type 1. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, primary hyperparathyroidism was single-gland disease in 47% of parathyroidectomies versus 0% in genotype-positive multiple endocrine neoplasia type 1 index cases. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, 17% of duodenopancreatic neuroendocrine tumors were multifocal versus 68% in genotype-positive multiple endocrine neoplasia type 1 index cases. Genotype-negative patients with clinical multiple endocrine neoplasia type 1 had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas. Conclusion: Genotype-negative patients with clinical multiple endocrine neoplasia type 1 have a different clinical course than genotype-positive multiple endocrine neoplasia type 1 index cases. This may support a separate classification and a tailored surveillance regimen. Of the genotype-negative patients with clinical multiple endocrine neoplasia type 1 who had parathyroidectomy, almost half had no evidence of multigland disease and may be potential candidates for a more targeted single-gland approach.
AB - Background: It is unclear whether genotype-negative clinical multiple endocrine neoplasia type 1 patients derive equal benefit from prospective surveillance as genotype-positive patients. Methods: In this retrospective cohort study, we compared genotype-negative patients with clinical multiple endocrine neoplasia type 1 with genotype-positive index cases. Primary outcome was age-related penetrance of manifestations; secondary outcomes were disease-specific survival and clinical course of endocrine tumors. Results: We included 39 genotype-negative patients with clinical multiple endocrine neoplasia type 1 (Male: 33%) and 63 genotype-positive multiple endocrine neoplasia type 1 index cases (Male: 59%). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were 65 years old at last follow-up; genotype-positive multiple endocrine neoplasia type 1 index cases were 50 (P <.001). Genotype-negative patients with clinical multiple endocrine neoplasia type 1 were significantly older at their first and second primary manifestation. Only 1 developed a third primary manifestation. No genotype-negative patients with clinical multiple endocrine neoplasia type 1 with primary hyperparathyroidism and a pituitary adenoma developed a duodenopancreatic neuroendocrine tumor. Disease-specific survival was significantly better in genotype-negative patients with clinical multiple endocrine neoplasia type 1. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, primary hyperparathyroidism was single-gland disease in 47% of parathyroidectomies versus 0% in genotype-positive multiple endocrine neoplasia type 1 index cases. In genotype-negative patients with clinical multiple endocrine neoplasia type 1, 17% of duodenopancreatic neuroendocrine tumors were multifocal versus 68% in genotype-positive multiple endocrine neoplasia type 1 index cases. Genotype-negative patients with clinical multiple endocrine neoplasia type 1 had more pituitary macroadenomas, fewer prolactinomas, and more somatotroph adenomas. Conclusion: Genotype-negative patients with clinical multiple endocrine neoplasia type 1 have a different clinical course than genotype-positive multiple endocrine neoplasia type 1 index cases. This may support a separate classification and a tailored surveillance regimen. Of the genotype-negative patients with clinical multiple endocrine neoplasia type 1 who had parathyroidectomy, almost half had no evidence of multigland disease and may be potential candidates for a more targeted single-gland approach.
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U2 - 10.1016/j.surg.2020.04.067
DO - 10.1016/j.surg.2020.04.067
M3 - Article
C2 - 32703679
AN - SCOPUS:85088241167
SN - 0039-6060
VL - 169
SP - 175
EP - 184
JO - Surgery (United States)
JF - Surgery (United States)
IS - 1
ER -