Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

Louise Volund Larsen; Delphine Mirebeau-Prunier; Tsuneo Imai; Cristina Alvarez-Escola; Kornelia Hasse-Lazar; Simona Censi; Luciana A. Castroneves; Akihiro Sakurai; Minoru Kihara; Kiyomi Horiuchi; Veronique Dorine Barbu; Francoise Borson-Chazot; Anne-Paule Gimenez-Roqueplo; Pascal Pigny; Stephane Pinson; Nelson Wohllk; Charis Eng; Berna Imge Aydogan; Dhananjaya Saranath; Sarka Dvorakova; Frederic Castinetti; Attila Patocs; Damijan Bergant; Thera P. Links; Mariola Peczkowska; Ana O. Hoff; Caterina Mian; Trisha Dwight; Barbara Jarzab; Hartmut P. H. Neumann; Mercedes Robledo; Shinya Uchino; Anne Barlier; Christian Godballe; Jes Sloth Mathiesen

doi:10.1530/EC-20-0163

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

Louise Volund Larsen
, Delphine Mirebeau-Prunier
, Tsuneo Imai
, Cristina Alvarez-Escola
, Kornelia Hasse-Lazar
, Simona Censi
, Luciana A. Castroneves
, Akihiro Sakurai
, Minoru Kihara
, Kiyomi Horiuchi
, Veronique Dorine Barbu
, Francoise Borson-Chazot
, Anne-Paule Gimenez-Roqueplo
, Pascal Pigny
, Stephane Pinson
, Nelson Wohllk
, Charis Eng
, Berna Imge Aydogan
, Dhananjaya Saranath
, Sarka Dvorakova

Frederic Castinetti, Attila Patocs, Damijan Bergant, Thera P. Links, Mariola Peczkowska, Ana O. Hoff, Caterina Mian, Trisha Dwight, Barbara Jarzab, Hartmut P. H. Neumann, Mercedes Robledo, Shinya Uchino, Anne Barlier, Christian Godballe, Jes Sloth Mathiesen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

33 Citations (Scopus)

130 Downloads (Pure)

Abstract

Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PH PT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.

Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017.

Results: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.

Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PH PT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

Original language	English
Pages (from-to)	489-497
Number of pages	9
Journal	Endocrine Connections
Volume	9
Issue number	6
DOIs	https://doi.org/10.1530/EC-20-0163
Publication status	Published - Jun-2020

Keywords

primary hyperparathyroidism
multiple endocrine neoplasia type 2A
RET
medullary thyroid carcinoma
pheochromocytoma
MEDULLARY-THYROID CARCINOMA
RET PROTOONCOGENE
SURGICAL-MANAGEMENT
PROGNOSTIC-FACTORS
DISEASE PHENOTYPE
CODON 634
MEN 2A
MUTATIONS
PHEOCHROMOCYTOMA
PREVALENCE

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Larsen, L. V., Mirebeau-Prunier, D., Imai, T., Alvarez-Escola, C., Hasse-Lazar, K., Censi, S., Castroneves, L. A., Sakurai, A., Kihara, M., Horiuchi, K., Barbu, V. D., Borson-Chazot, F., Gimenez-Roqueplo, A.-P., Pigny, P., Pinson, S., Wohllk, N., Eng, C., Aydogan, B. I., Saranath, D., ... Mathiesen, J. S. (2020). Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study. Endocrine Connections, 9(6), 489-497. https://doi.org/10.1530/EC-20-0163

@article{03b60427773f454392b90d29968f11eb,

title = "Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study",

abstract = "Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PH PT) in up to 30\% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017.Results: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9\% (95\% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PH PT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.",

keywords = "primary hyperparathyroidism, multiple endocrine neoplasia type 2A, RET, medullary thyroid carcinoma, pheochromocytoma, MEDULLARY-THYROID CARCINOMA, RET PROTOONCOGENE, SURGICAL-MANAGEMENT, PROGNOSTIC-FACTORS, DISEASE PHENOTYPE, CODON 634, MEN 2A, MUTATIONS, PHEOCHROMOCYTOMA, PREVALENCE",

author = "Larsen, \{Louise Volund\} and Delphine Mirebeau-Prunier and Tsuneo Imai and Cristina Alvarez-Escola and Kornelia Hasse-Lazar and Simona Censi and Castroneves, \{Luciana A.\} and Akihiro Sakurai and Minoru Kihara and Kiyomi Horiuchi and Barbu, \{Veronique Dorine\} and Francoise Borson-Chazot and Anne-Paule Gimenez-Roqueplo and Pascal Pigny and Stephane Pinson and Nelson Wohllk and Charis Eng and Aydogan, \{Berna Imge\} and Dhananjaya Saranath and Sarka Dvorakova and Frederic Castinetti and Attila Patocs and Damijan Bergant and Links, \{Thera P.\} and Mariola Peczkowska and Hoff, \{Ana O.\} and Caterina Mian and Trisha Dwight and Barbara Jarzab and Neumann, \{Hartmut P. H.\} and Mercedes Robledo and Shinya Uchino and Anne Barlier and Christian Godballe and Mathiesen, \{Jes Sloth\}",

year = "2020",

month = jun,

doi = "10.1530/EC-20-0163",

language = "English",

volume = "9",

pages = "489--497",

journal = "Endocrine Connections",

issn = "2049-3614",

publisher = "BIOSCIENTIFICA LTD",

number = "6",

}

Larsen, LV, Mirebeau-Prunier, D, Imai, T, Alvarez-Escola, C, Hasse-Lazar, K, Censi, S, Castroneves, LA, Sakurai, A, Kihara, M, Horiuchi, K, Barbu, VD, Borson-Chazot, F, Gimenez-Roqueplo, A-P, Pigny, P, Pinson, S, Wohllk, N, Eng, C, Aydogan, BI, Saranath, D, Dvorakova, S, Castinetti, F, Patocs, A, Bergant, D, Links, TP, Peczkowska, M, Hoff, AO, Mian, C, Dwight, T, Jarzab, B, Neumann, HPH, Robledo, M, Uchino, S, Barlier, A, Godballe, C & Mathiesen, JS 2020, 'Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study', Endocrine Connections, vol. 9, no. 6, pp. 489-497. https://doi.org/10.1530/EC-20-0163

TY - JOUR

T1 - Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A

T2 - an international multicenter study

AU - Larsen, Louise Volund

AU - Mirebeau-Prunier, Delphine

AU - Imai, Tsuneo

AU - Alvarez-Escola, Cristina

AU - Hasse-Lazar, Kornelia

AU - Censi, Simona

AU - Castroneves, Luciana A.

AU - Sakurai, Akihiro

AU - Kihara, Minoru

AU - Horiuchi, Kiyomi

AU - Barbu, Veronique Dorine

AU - Borson-Chazot, Francoise

AU - Gimenez-Roqueplo, Anne-Paule

AU - Pigny, Pascal

AU - Pinson, Stephane

AU - Wohllk, Nelson

AU - Eng, Charis

AU - Aydogan, Berna Imge

AU - Saranath, Dhananjaya

AU - Dvorakova, Sarka

AU - Castinetti, Frederic

AU - Patocs, Attila

AU - Bergant, Damijan

AU - Links, Thera P.

AU - Peczkowska, Mariola

AU - Hoff, Ana O.

AU - Mian, Caterina

AU - Dwight, Trisha

AU - Jarzab, Barbara

AU - Neumann, Hartmut P. H.

AU - Robledo, Mercedes

AU - Uchino, Shinya

AU - Barlier, Anne

AU - Godballe, Christian

AU - Mathiesen, Jes Sloth

PY - 2020/6

Y1 - 2020/6

N2 - Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PH PT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017.Results: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PH PT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

AB - Objective: Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PH PT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases.Design and methods: An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017.Results: Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4-1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis.Conclusions: Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PH PT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

KW - primary hyperparathyroidism

KW - multiple endocrine neoplasia type 2A

KW - RET

KW - medullary thyroid carcinoma

KW - pheochromocytoma

KW - MEDULLARY-THYROID CARCINOMA

KW - RET PROTOONCOGENE

KW - SURGICAL-MANAGEMENT

KW - PROGNOSTIC-FACTORS

KW - DISEASE PHENOTYPE

KW - CODON 634

KW - MEN 2A

KW - MUTATIONS

KW - PHEOCHROMOCYTOMA

KW - PREVALENCE

U2 - 10.1530/EC-20-0163

DO - 10.1530/EC-20-0163

M3 - Article

SN - 2049-3614

VL - 9

SP - 489

EP - 497

JO - Endocrine Connections

JF - Endocrine Connections

IS - 6

ER -

Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

Abstract

Keywords

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