PMID- 26751192
OWN - NLM
STAT- MEDLINE
DCOM- 20160815
LR  - 20160304
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 101
IP  - 3
DP  - 2016 Mar
TI  - Impact of Delay in Diagnosis in Outcomes in MEN1: Results From the Dutch MEN1 
      Study Group.
PG  - 1159-65
LID - 10.1210/jc.2015-3766 [doi]
AB  - OBJECTIVE: Identifying a germline mutation in the multiple endocrine neoplasia 
      type 1 (MEN1) gene in an index case has consequences for a whole family. Eligible 
      family members should be offered genetic counseling and MEN1 mutation testing. 
      Subsequently, clinical screening of mutation carriers according to the guidelines 
      should be initiated. We assessed whether there is a lag time from MEN1 diagnosis 
      of the index case to MEN1 diagnosis of family members. In addition, we determined 
      whether this lag time was associated with an increased morbidity and mortality 
      risk. DESIGN: A cohort study was performed using the Dutch MEN1 database, 
      including >90% of the Dutch MEN1 population >16 years of age (n = 393). RESULTS: 
      Fifty-eight MEN1 families were identified, of whom 57 were index cases and 247 
      were non-index cases (n = 304). The median lag time in MEN1 diagnosis of family 
      members was 3.5 (range, 0-30) years. At the time of MEN1 diagnosis, 30 (12.1%) 
      non-index cases had a duodenopancreatic neuroendocrine tumor, of whom 20% had 
      metastases with a mean lag time of 10.9 years, in comparison with 7.1 years 
      without metastases. Twenty-five (10.1%) non-index cases had a pituitary tumor, of 
      whom 80% had a microadenoma and 20% had a macroadenoma, with mean lag times of 
      7.2 and 10.6 years, respectively. Ninety-five (38.4%) non-index cases had a 
      primary hyperparathyroidism with a mean lag time of 9.5 years in comparison with 
      seven patients without a primary hyperparathyroidism with a mean lag time of 3 
      years (P = .005). Ten non-index cases died because of a MEN1-related cause that 
      developed during or before the lag time. CONCLUSION: There is a clinically 
      relevant delay in MEN1 diagnosis in families because of a lag time between the 
      diagnosis of an index case and the rest of the family. More emphasis should be 
      placed on the conduct of proper counseling and genetic testing in all eligible 
      family members.
FAU - van Leeuwaarde, Rachel S
AU  - van Leeuwaarde RS
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - van Nesselrooij, Bernadette P M
AU  - van Nesselrooij BP
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Hermus, Ad R
AU  - Hermus AR
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Dekkers, Olaf M
AU  - Dekkers OM
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - de Herder, Wouter W
AU  - de Herder WW
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - van der Horst-Schrivers, Anouk N
AU  - van der Horst-Schrivers AN
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Drent, Madeleine L
AU  - Drent ML
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Bisschop, Peter H
AU  - Bisschop PH
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Havekes, Bas
AU  - Havekes B
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Vriens, Menno R
AU  - Vriens MR
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - de Laat, Joanne M
AU  - de Laat JM
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Pieterman, Carolina R C
AU  - Pieterman CR
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
FAU - Valk, Gerlof D
AU  - Valk GD
AD  - Departments of Endocrine Oncology (R.S.v.L., J.M.d.L., C.R.C.P., G.D.V.) and 
      Clinical Genetics (B.P.M.v.N.), University Medical Center Utrecht, 3584 CX 
      Utrecht, The Netherlands; Department of Endocrinology (A.R.H.), Radboud 
      University Medical Center, 6525 GA Nijmegen, The Netherlands; Departments of 
      Endocrinology and Metabolism and Clinical Epidemiology (O.M.D.), Leiden 
      University Medical Center, 2333 ZA Leiden, The Netherlands; Department of 
      Clinical Epidemiology (O.M.D.), Aarhus University, 8000 Aarhus, Denmark; 
      Department of Internal Medicine (W.W.d.H.), Erasmus Medical Center, 3015 CE 
      Rotterdam, The Netherlands; Department of Endocrinology (A.N.v.d.H.-S.), 
      University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; 
      Department of Internal Medicine (M.L.D.), Section of Endocrinology, VU University 
      Medical Center, 1081 HZ Amsterdam, The Netherlands; Department of Endocrinology 
      and Metabolism (P.H.B.), Academic Medical Center, 1105 AZ Amsterdam, The 
      Netherlands; Department of Internal Medicine (B.H.), Division of Endocrinology, 
      Maastricht University Medical Center, 6229 GT Maastricht, The Netherlands; and 
      Department of Endocrine Surgery (M.R.V.), University Medical Center Utrecht, 3584 
      CX Utrecht, The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160111
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Child
MH  - Delayed Diagnosis/*statistics & numerical data
MH  - Family
MH  - Female
MH  - Genetic Testing/*statistics & numerical data
MH  - Germ-Line Mutation
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Morbidity
MH  - Multiple Endocrine Neoplasia Type 1/*diagnosis/*epidemiology/genetics
MH  - Netherlands/epidemiology
MH  - Prognosis
MH  - Proto-Oncogene Proteins/genetics
MH  - Survival Analysis
MH  - Young Adult
EDAT- 2016/01/12 06:00
MHDA- 2016/08/16 06:00
CRDT- 2016/01/12 06:00
PHST- 2016/01/12 06:00 [entrez]
PHST- 2016/01/12 06:00 [pubmed]
PHST- 2016/08/16 06:00 [medline]
AID - 10.1210/jc.2015-3766 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2016 Mar;101(3):1159-65. doi: 10.1210/jc.2015-3766. Epub 
      2016 Jan 11.