Adrenal nodularity and somatic mutations in primary aldosteronism

One node is the culprit?

T. Dekkers, M. Ter Meer, J. W.M. Lenders, A. R.M. Hermus, L. Schultze Kool, J. F. Langenhuijsen, K. Nishimoto, Tadashi Ogishima, K. Mukai, E. A.B. Azizan, B. Tops, J. Deinum, B. Küsters

研究成果: ジャーナルへの寄稿記事

66 引用 (Scopus)

抄録

Context: Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. Objective: The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. Design and Methods: We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. Results: Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. Conclusions: Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.

元の言語英語
ジャーナルJournal of Clinical Endocrinology and Metabolism
99
発行部数7
DOI
出版物ステータス出版済み - 1 1 2014

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Hyperaldosteronism
Aldosterone
Adenoma
Mutation
Genes
Adrenal Glands
Ports and harbors
Hyperplasia
Hydrocortisone
Zona Fasciculata
Zona Glomerulosa
Calcium
Adrenal Cortex
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

これを引用

Dekkers, T., Ter Meer, M., Lenders, J. W. M., Hermus, A. R. M., Schultze Kool, L., Langenhuijsen, J. F., ... Küsters, B. (2014). Adrenal nodularity and somatic mutations in primary aldosteronism: One node is the culprit? Journal of Clinical Endocrinology and Metabolism, 99(7). https://doi.org/10.1210/jc.2013-4255

Adrenal nodularity and somatic mutations in primary aldosteronism : One node is the culprit? / Dekkers, T.; Ter Meer, M.; Lenders, J. W.M.; Hermus, A. R.M.; Schultze Kool, L.; Langenhuijsen, J. F.; Nishimoto, K.; Ogishima, Tadashi; Mukai, K.; Azizan, E. A.B.; Tops, B.; Deinum, J.; Küsters, B.

:: Journal of Clinical Endocrinology and Metabolism, 巻 99, 番号 7, 01.01.2014.

研究成果: ジャーナルへの寄稿記事

Dekkers, T, Ter Meer, M, Lenders, JWM, Hermus, ARM, Schultze Kool, L, Langenhuijsen, JF, Nishimoto, K, Ogishima, T, Mukai, K, Azizan, EAB, Tops, B, Deinum, J & Küsters, B 2014, 'Adrenal nodularity and somatic mutations in primary aldosteronism: One node is the culprit?', Journal of Clinical Endocrinology and Metabolism, 巻. 99, 番号 7. https://doi.org/10.1210/jc.2013-4255
Dekkers, T. ; Ter Meer, M. ; Lenders, J. W.M. ; Hermus, A. R.M. ; Schultze Kool, L. ; Langenhuijsen, J. F. ; Nishimoto, K. ; Ogishima, Tadashi ; Mukai, K. ; Azizan, E. A.B. ; Tops, B. ; Deinum, J. ; Küsters, B. / Adrenal nodularity and somatic mutations in primary aldosteronism : One node is the culprit?. :: Journal of Clinical Endocrinology and Metabolism. 2014 ; 巻 99, 番号 7.
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abstract = "Context: Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. Objective: The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. Design and Methods: We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. Results: Glands contained a solitary adenoma in 43{\%} and nodular hyperplasia in 53{\%} of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. Conclusions: Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.",
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T1 - Adrenal nodularity and somatic mutations in primary aldosteronism

T2 - One node is the culprit?

AU - Dekkers, T.

AU - Ter Meer, M.

AU - Lenders, J. W.M.

AU - Hermus, A. R.M.

AU - Schultze Kool, L.

AU - Langenhuijsen, J. F.

AU - Nishimoto, K.

AU - Ogishima, Tadashi

AU - Mukai, K.

AU - Azizan, E. A.B.

AU - Tops, B.

AU - Deinum, J.

AU - Küsters, B.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Context: Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. Objective: The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. Design and Methods: We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. Results: Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. Conclusions: Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.

AB - Context: Somatic mutations in genes that influence cell entry of calcium have been identified in aldosterone-producing adenomas (APAs) of adrenal cortex in primary aldosteronism (PA). Many adrenal glands removed for suspicion of APA do not contain a single adenoma but nodular hyperplasia. Objective: The objective of the study was to assess multinodularity and phenotypic and genotypic characteristics of adrenals removed because of the suspicion of APAs. Design and Methods: We assessed the adrenals of 53 PA patients for histopathological characteristics and immunohistochemistry for aldosterone (P450C18) and cortisol (P450C11) synthesis and for KCNJ5, ATP1A1, ATP2B3, and CACNA1D mutations in microdissected nodi. Results: Glands contained a solitary adenoma in 43% and nodular hyperplasia in 53% of cases. Most adrenal glands contained only one nodule positive for P450C18 expression, with all other nodules negative. KCNJ5 mutations were present in 22 of 53 adrenals (13 adenoma and nine multinodular adrenals). An ATP1A1 and a CACNA1D mutation were found in one multinodular gland each and an ATP2B3 mutation in five APA-containing glands. Mutations were always located in the P450C18-positive nodule. In one gland two nodules containing two different KCNJ5 mutations were present. Zona fasciculata-like cells were more typical for KCNJ5 mutation-containing nodules and zona glomerulosa-like cells for the other three genes. Conclusions: Somatic mutations in KCNJ5, ATP1A1, or CACNA1D genes are not limited to APAs but are also found in the more frequent multinodular adrenals. In multinodular glands, only one nodule harbors a mutation. This suggests that the occurrence of a mutation and nodule formation are independent processes. The implications for clinical management remain to be determined.

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