PMID- 32311048 OWN - NLM STAT- MEDLINE DCOM- 20210201 LR - 20240328 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 105 IP - 6 DP - 2020 Jun 1 TI - Clinical MEN-1 Among a Large Cohort of Patients With Acromegaly. PG - e2271-81 LID - dgaa142 [pii] LID - 10.1210/clinem/dgaa142 [doi] AB - CONTEXT: Clinical multiple endocrine neoplasia type 1 (MEN-1) is diagnosed by the presence of at least 2 MEN-1-associated tumors. Many patients with acromegaly and clinical MEN-1 yield negative testing for MEN1 mutations. While cases of acromegaly and primary hyperparathyroidism (PHP) with negative genetic testing have been reported, its prevalence among patients with acromegaly is undetermined, and the clinical presentation has not been well characterized. OBJECTIVES: The main goals of this study are: (1) To determine the prevalence of clinical MEN-1 with PHP in patients with acromegaly and characterize their clinical features; and (2) to evaluate the genetic basis for the coexistence of acromegaly and PHP. DESIGN: Retrospective record review and genetic analysis. SETTING: Clinical Research Centers. PARTICIPANTS: 414 patients with acromegaly. INTERVENTIONS: Clinical evaluation and DNA sequencing for MEN1, CDKN1A, CDKN1B, CDKN2B, CDKN2C, and AIP genes. MAIN OUTCOME MEASUREMENTS: Clinical and genetic analysis. RESULTS: Among patients with acromegaly, clinical MEN-1, as defined by the presence of at least one other MEN-1-associated tumor, was present in 6.6%. PHP occurred in 6.1%; more than half had parathyroid hyperplasia. DNA sequencing was unrevealing for genetic mutations, except for 1 case of a CDC73 mutation. Acromegaly was diagnosed at an older age with a higher prevalence of malignancies (specifically breast and thyroid) in patients with coexisting PHP than those with isolated acromegaly. CONCLUSIONS: A distinct phenotype is described in patients with clinical MEN-1 and negative genetic testing for mutations previously associated with this syndrome. Further studies are needed to identify other genes that may explain the association between PHP and acromegaly. CI - (c) Endocrine Society 2020. FAU - Nachtigall, Lisa B AU - Nachtigall LB AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Guarda, Francisco J AU - Guarda FJ AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. AD - Endocrinology Department and Center for Translational Endocrinology (CETREN), School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile. FAU - Lines, Kate E AU - Lines KE AD - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK. FAU - Ghajar, Alireza AU - Ghajar A AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Dichtel, Laura AU - Dichtel L AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Mumbach, Giselle AU - Mumbach G AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Zhao, Wenxiu AU - Zhao W AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Zhang, Xun AU - Zhang X AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Tritos, Nicholas A AU - Tritos NA AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Swearingen, Brooke AU - Swearingen B AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Miller, Karen K AU - Miller KK AD - Neuroendocrine Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts. FAU - Thakker, Rajesh V AU - Thakker RV AD - Academic Endocrine Unit, OCDEM, Radcliffe Department of Medicine, University of Oxford, Churchill Hospital, Oxford, UK. LA - eng GR - WT_/Wellcome Trust/United Kingdom GR - K23 DK113220/DK/NIDDK NIH HHS/United States GR - K24 HL092902/HL/NHLBI NIH HHS/United States GR - DH_/Department of Health/United Kingdom PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Biomarkers) RN - 0 (MEN1 protein, human) RN - 0 (Proto-Oncogene Proteins) SB - IM MH - Acromegaly/*complications MH - Adult MH - Aged MH - Aged, 80 and over MH - Biomarkers/*analysis MH - Female MH - Follow-Up Studies MH - Humans MH - Hyperparathyroidism, Primary/*etiology/pathology MH - Male MH - Middle Aged MH - Multiple Endocrine Neoplasia Type 1/*etiology/pathology MH - Mutation MH - Phenotype MH - Prognosis MH - Proto-Oncogene Proteins/*genetics MH - Retrospective Studies MH - Young Adult PMC - PMC7180000 OTO - NOTNLM OT - MEN-1 phenocopy OT - acromegaly OT - hyperparathyroidism OT - multiple endocrine neoplasia type 1 (MEN-1) EDAT- 2020/04/21 06:00 MHDA- 2021/02/02 06:00 PMCR- 2020/04/20 CRDT- 2020/04/21 06:00 PHST- 2020/01/27 00:00 [received] PHST- 2020/04/01 00:00 [accepted] PHST- 2020/04/21 06:00 [pubmed] PHST- 2021/02/02 06:00 [medline] PHST- 2020/04/21 06:00 [entrez] PHST- 2020/04/20 00:00 [pmc-release] AID - 5822884 [pii] AID - dgaa142 [pii] AID - 10.1210/clinem/dgaa142 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2020 Jun 1;105(6):e2271-81. doi: 10.1210/clinem/dgaa142.