International Histopathology Consensus for Unilateral Primary Aldosteronism

Tracy Ann Williams; Celso E Gomez-Sanchez; William E Rainey; Thomas J Giordano; Alfred K Lam; Alison Marker; Ozgur Mete; Yuto Yamazaki; Maria Claudia Nogueira Zerbini; Felix Beuschlein; Fumitoshi Satoh; Jacopo Burrello; Holger Schneider; Jacques W M Lenders; Paolo Mulatero; Isabella Castellano; Thomas Knösel; Mauro Papotti; Wolfgang Saeger; Hironobu Sasano; Martin Reincke

doi:10.1210/clinem/dgaa484

International Histopathology Consensus for Unilateral Primary Aldosteronism

J Clin Endocrinol Metab. 2021 Jan 1;106(1):42-54. doi: 10.1210/clinem/dgaa484.

Authors

Tracy Ann Williams^{1

2}, Celso E Gomez-Sanchez³, William E Rainey^{4

5}, Thomas J Giordano^{5

6}, Alfred K Lam⁷, Alison Marker⁸, Ozgur Mete^{9

10}, Yuto Yamazaki¹¹, Maria Claudia Nogueira Zerbini¹², Felix Beuschlein^{1

13}, Fumitoshi Satoh¹⁴, Jacopo Burrello², Holger Schneider¹, Jacques W M Lenders^{15

16}, Paolo Mulatero², Isabella Castellano¹⁷, Thomas Knösel¹⁸, Mauro Papotti¹⁹, Wolfgang Saeger²⁰, Hironobu Sasano¹¹, Martin Reincke¹

Affiliations

¹ Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Germany.
² Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Turin, Turin, Italy.
³ Endocrine Division, G.V. (Sonny) Montgomery VA Medical Center, and Department of Pharmacology and Toxicology and Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁴ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
⁵ Division of Metabolism, Endocrine, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Pathology and Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
⁷ School of Medicine, Griffith University, Gold Coast, Australia.
⁸ Department of Histopathology, Cambridge University NHS Foundation Trust, Cambridge, UK.
⁹ Department of Pathology, University Health Network, Toronto, Canada.
¹⁰ Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
¹¹ Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹² Departamento de Patologia, Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil.
¹³ Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich, Switzerland.
¹⁴ Division of Clinical Hypertension, Endocrinology and Metabolism, Tohoku University Graduate School of Medicine, Sendai, Japan.
¹⁵ Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁶ Department of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
¹⁷ Division of Pathology, Department of Medical Sciences, University of Turin, Turin, Italy.
¹⁸ Institute of Pathology, Ludwig-Maximilians-Universität München, Germany.
¹⁹ Department of Oncology, University of Turin, Turin, Italy.
²⁰ Institute of Pathology, Universität Hamburg, Germany.

Abstract

Objective: Develop a consensus for the nomenclature and definition of adrenal histopathologic features in unilateral primary aldosteronism (PA).

Context: Unilateral PA is the most common surgically treated form of hypertension. Morphologic examination combined with CYP11B2 (aldosterone synthase) immunostaining reveals diverse histopathologic features of lesions in the resected adrenals.

Patients and methods: Surgically removed adrenals (n = 37) from 90 patients operated from 2015 to 2018 in Munich, Germany, were selected to represent the broad histologic spectrum of unilateral PA. Five pathologists (Group 1 from Germany, Italy, and Japan) evaluated the histopathology of hematoxylin-eosin (HE) and CYP11B2 immunostained sections, and a consensus was established to define the identifiable features. The consensus was subsequently used by 6 additional pathologists (Group 2 from Australia, Brazil, Canada, Japan, United Kingdom, United States) for the assessment of all adrenals with disagreement for histopathologic diagnoses among group 1 pathologists.

Results: Consensus was achieved to define histopathologic features associated with PA. Use of CYP11B2 immunostaining resulted in a change of the original HE morphology-driven diagnosis in 5 (14%) of 37 cases. Using the consensus criteria, group 2 pathologists agreed for the evaluation of 11 of the 12 cases of disagreement among group 1 pathologists.

Conclusion: The HISTALDO (histopathology of primary aldosteronism) consensus is useful to standardize nomenclature and achieve consistency among pathologists for the histopathologic diagnosis of unilateral PA. CYP11B2 immunohistochemistry should be incorporated into the routine clinical diagnostic workup to localize the likely source of aldosterone production.

Keywords: CYP11B2; adrenal gland; diagnostic histopathology; immunohistochemistry; primary aldosteronism.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Validation Study

MeSH terms

Adrenal Glands / metabolism
Adrenal Glands / pathology
Adrenalectomy / methods
Adrenalectomy / standards
Adult
Cohort Studies
Consensus
Cytochrome P-450 CYP11B2 / metabolism
Cytodiagnosis / methods
Cytodiagnosis / standards
Diagnostic Techniques, Endocrine / standards*
Female
Germany
Histological Techniques / standards*
Humans
Hyperaldosteronism / complications
Hyperaldosteronism / diagnosis*
Hyperaldosteronism / surgery
Hypertension / diagnosis
Hypertension / etiology
Hypertension / surgery
Immunohistochemistry
Internationality
Male
Middle Aged
Practice Guidelines as Topic / standards
Societies, Medical / standards

Substances

Cytochrome P-450 CYP11B2

Abstract

Publication types

MeSH terms

Substances

Grants and funding