Distinguishing different subtypes of aldosterone-producing adenoma by histological, immunohistochemical and radiological features; a basis for individualised treatment strategies in primary aldosteronism?

Andrew S Powlson; Ada Teo; Lalarukh Haris; Carmela Maniero; Alison Marker; Elena Azizan; Mark Gurnell; Morris J Brown

doi:10.1530/endoabs.38.P212

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Endocrine Abstracts (2015) 38 P212 | DOI: 10.1530/endoabs.38.P212

SFEBES2015 Poster Presentations Obesity, diabetes, metabolism and cardiovascular (108 abstracts)

Distinguishing different subtypes of aldosterone-producing adenoma by histological, immunohistochemical and radiological features; a basis for individualised treatment strategies in primary aldosteronism?

Andrew S Powlson ¹ , Ada Teo ² , Lalarukh Haris ² , Carmela Maniero ² , Alison Marker ³ , Elena Azizan ² , Mark Gurnell ¹ & Morris J Brown ²

Err

Author affiliations

¹Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, UK; ²Clinical Pharmacology Unit, University of Cambridge, Cambridge, UK; ³Department of Pathology, Addenbrooke’s Hospital, Cambridge, UK.

Background: Primary aldosteronism (PA) is now recognised to account for 5–10% of all cases of hypertension (and 20–25% of refractory hypertension). For patients with a demonstrable unilateral cause, adrenalectomy offers the potential for cure of PA, although resolution of hypertension occurs in only ~50% of patients. We have examined histological appearances and radiological features in patients with APAs undergoing adrenalectomy in an attempt to further our understanding of the heterogeneity of PA.

Methods/results: We report 2 years’ experience since our retrospective analysis of >50 APAs, after which we introduced routine post-operative immunohistochemistry, and during which time PET-CT has started to provide an in vivo assessment of function. Histological examination of adrenalectomy specimens identified two distinct subtypes of APA; those resembling cells of the zona fasciculata (ZF) (Fig. 1a), and those harbouring more compact cells reminiscent of the zona glomerulosa (ZG) (Fig. 2a). ZF tumours are larger, with lipid-laden cells, and may represent the original Conn’s adenoma. In contrast, ZG tumours are often smaller (and may not be easily visualised on CT or MRI), with lipid-deplete cells. IHC using CYP11B1 and CYP11B2 selective antibodies confirms predominant CYP11B1 expression in ZF tumours (Fig. 1b); in contrast, ZG tumours express mainly CYP11B2 (Fig. 2c). Preliminary findings suggest that these different tumour subtypes may exhibit differing uptake of the PET tracer 11C-metomidate (ZG>ZF).

Conclusions: The identification of different histological subtypes, together with recent advances in tumour genotyping and functional PET imaging, may now provide an opportunity to investigate stratified decision-making in the management of PA, thus targeting limited resources towards those patients who are likely to benefit most from adrenalectomy.