Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study

doi:10.2147/CLEP.S174606

. 2018 Oct 12:10:1479-1487.

doi: 10.2147/CLEP.S174606. eCollection 2018.

Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study

Jes Sloth Mathiesen^{1

2}, Jens Peter Kroustrup³, Peter Vestergaard^{3

4}, Kirstine Stochholm^{5

6}, Per Løgstrup Poulsen⁵, Åse Krogh Rasmussen⁷, Ulla Feldt-Rasmussen⁷, Sten Schytte⁸, Henrik Baymler Pedersen⁹, Christoffer Holst Hahn¹⁰, Jens Bentzen¹¹, Sören Möller^{2

12}, Mette Gaustadnes¹³, Maria Rossing¹⁴, Finn Cilius Nielsen¹⁴, Kim Brixen², Anja Lisbeth Frederiksen^{2

15}, Christian Godballe¹

Affiliations

¹ Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark, jes_mathiesen@yahoo.dk.
² Department of Clinical Research, University of Southern Denmark, Odense, Denmark, jes_mathiesen@yahoo.dk.
³ Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
⁴ Steno Diabetes Center North Jutland, Aalborg, Denmark.
⁵ Department of Internal Medicine and Endocrinology, Aarhus University Hospital, DK-8000 Aarhus, Denmark.
⁶ Center for Rare Diseases, Aarhus University Hospital, Aarhus N, Denmark.
⁷ Department of Medical Endocrinology, Copenhagen University Hospital, Copenhagen, Denmark.
⁸ Department of ORL Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark.
⁹ Department of ORL Head and Neck Surgery, Aalborg University Hospital, Aalborg, Denmark.
¹⁰ Department of ORL Head and Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark.
¹¹ Department of Oncology, Herlev Hospital, Herlev, Denmark.
¹² Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
¹³ Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
¹⁴ Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁵ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

PMID: 30349395
PMCID: PMC6190626
DOI: 10.2147/CLEP.S174606

Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study

Jes Sloth Mathiesen et al. Clin Epidemiol. 2018.

. 2018 Oct 12:10:1479-1487.

doi: 10.2147/CLEP.S174606. eCollection 2018.

Authors

Affiliations

¹ Department of ORL Head & Neck Surgery and Audiology, Odense University Hospital, Odense, Denmark, jes_mathiesen@yahoo.dk.
² Department of Clinical Research, University of Southern Denmark, Odense, Denmark, jes_mathiesen@yahoo.dk.
³ Department of Clinical Medicine and Endocrinology, Aalborg University Hospital, Aalborg, Denmark.
⁴ Steno Diabetes Center North Jutland, Aalborg, Denmark.
⁵ Department of Internal Medicine and Endocrinology, Aarhus University Hospital, DK-8000 Aarhus, Denmark.
⁶ Center for Rare Diseases, Aarhus University Hospital, Aarhus N, Denmark.
⁷ Department of Medical Endocrinology, Copenhagen University Hospital, Copenhagen, Denmark.
⁸ Department of ORL Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark.
⁹ Department of ORL Head and Neck Surgery, Aalborg University Hospital, Aalborg, Denmark.
¹⁰ Department of ORL Head and Neck Surgery, Copenhagen University Hospital, Copenhagen, Denmark.
¹¹ Department of Oncology, Herlev Hospital, Herlev, Denmark.
¹² Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark.
¹³ Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
¹⁴ Center for Genomic Medicine, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁵ Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.

PMID: 30349395
PMCID: PMC6190626
DOI: 10.2147/CLEP.S174606

Abstract

Background: The incidence and prevalence of multiple endocrine neoplasia 2A (MEN2A) have only been reported once in a nationwide setting. However, it is unclear whether the figures are representative of other populations, as the major component of the syndrome, hereditary medullary thyroid carcinoma (MTC), has been reported as rare in the same country. We conducted a nationwide retrospective cohort study of MEN2A in Denmark from 1901 to 2014, aiming to describe the incidence and prevalence.

Methods: This study included 250 unique MEN2A patients born or resident in Denmark before December 31, 2014. Patients were identified through the Danish REarranged during Transfection (RET) cohort, linkage of MEN2A pedigrees, the Danish MTC cohort, a nationwide collaboration of MEN2 centers, cross-checking of other relevant cohorts, and a systematic literature search.

Results: The incidence from 1971 to 2000 was 28 (95% CI: 21-37) per million live births per year. Incidence for the specific mutations or for the overall MEN2A group did not change significantly from 1901 to 2014 (P>0.05). Point prevalence at January 1, 2015, was 24 per million (95% CI: 20-28).

Conclusion: The incidence and prevalence of MEN2A in Denmark seem higher than those reported in other countries. This is likely explained by the Danish C611Y founder effect. Also, our data indicate no significant change in MEN2A incidence during the last century.

Keywords: Denmark; incidence; multiple endocrine neoplasia 2A; prevalence.

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Conflict of interest statement

Disclosure The authors report no conflict of interest in this work.

Figures

**Figure 1**
Flow chart showing identification of MEN2A patients. Dotted boxes indicate methods used and additional MEN2A patients for inclusion. **Notes:** ^aCopenhagen University Hospital, Aarhus University Hospital, Odense University Hospital, and Aalborg University Hospital. ^bDanish MTC cohort, pheochromocytoma cohort, hyperparathyroidism cohort, Hirschsprung cohort, multiple endocrine neoplasia cohort, and lichen amyloidosis cohort. **Abbreviations:** MEN2A, multiple endocrine neoplasia 2A; *RET*, Rearranged during Transfection.

**Figure 2**
Point prevalence of multiple endocrine neoplasia 2A in Denmark at January 1 according to years.

See this image and copyright information in PMC

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[1] Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. - PMC - PubMed

[2] Wells SA, Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. - PMC - PubMed

[3] Machens A, Lorenz K, Sekulla C, et al. Molecular epidemiology of multiple endocrine neoplasia 2: implications for RET screening in the new millenium. Eur J Endocrinol. 2013;168(3):307–314. - PubMed

[4] Machens A, Lorenz K, Sekulla C, et al. Molecular epidemiology of multiple endocrine neoplasia 2: implications for RET screening in the new millenium. Eur J Endocrinol. 2013;168(3):307–314. - PubMed

[5] Mathiesen JS, Kroustrup JP, Vestergaard P, et al. Incidence and prevalence of multiple endocrine neoplasia 2B in Denmark: a nationwide study. Endocr Relat Cancer. 2017;24(7):L39–L42. - PubMed

[6] Mathiesen JS, Kroustrup JP, Vestergaard P, et al. Incidence and prevalence of multiple endocrine neoplasia 2B in Denmark: a nationwide study. Endocr Relat Cancer. 2017;24(7):L39–L42. - PubMed

[7] Znaczko A, Donnelly DE, Morrison PJ. Epidemiology, clinical features, and genetics of multiple endocrine neoplasia type 2B in a complete population. Oncologist. 2014;19(12):1284–1286. - PMC - PubMed

[8] Znaczko A, Donnelly DE, Morrison PJ. Epidemiology, clinical features, and genetics of multiple endocrine neoplasia type 2B in a complete population. Oncologist. 2014;19(12):1284–1286. - PMC - PubMed

[9] Opsahl EM, Brauckhoff M, Schlichting E, et al. A nationwide study of multiple endocrine neoplasia type 2a in Norway: predictive and prognostic factors for the clinical course of medullary thyroid carcinoma. Thyroid. 2016;26(9):1225–1238. - PubMed

[10] Opsahl EM, Brauckhoff M, Schlichting E, et al. A nationwide study of multiple endocrine neoplasia type 2a in Norway: predictive and prognostic factors for the clinical course of medullary thyroid carcinoma. Thyroid. 2016;26(9):1225–1238. - PubMed

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Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study

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Incidence and prevalence of multiple endocrine neoplasia 2A in Denmark 1901-2014: a nationwide study

Authors

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Abstract

Conflict of interest statement

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Abstract

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