Primary hyperaldosteronism: Beyond the distinction between hyperplasia vs. adenoma
Creators: name: Barbosa, Barbara
name: Taylor, David
name: Diaz-Cano, Salvador J.
Publisher: name: figshare
Year: 2019
Subjects: subject: Biomarkers
subject: 111601 Cell Physiology
subject: FOS: Basic medicine
subject: FOS: Basic medicine
subject: 110302 Clinical Chemistry (diagnostics)
subject: FOS: Clinical medicine
subject: FOS: Clinical medicine
subject: 110306 Endocrinology
subject: 110104 Medical Biochemistry: Lipids
subject: Pathology

description: Background: Primary hyperaldosteronism (PA) is a heterogeneous condition functionally defined by high aldosterone/renin levels and inappropriate failure of aldosterone to suppress in response to excessive salt and water load. Adrenal venous sampling (AVS) is considered the gold standard for lateralization of aldosterone production. This study aims to determine the pathology of unilaterally increased aldosterone hypersecretion and to correlate the serum steroid panel with the morphological findings. Method: Between 2007 and 2017, 156 patients presented with a confirmed diagnosis of PA. The patients investigated in 2016-2017 had steroid panel with positive functional lateralization and adrenalectomy in 23. The pre-operative results for K+, aldosterone, and cortisol basal levels and after 240 minutes of salt and water overload, the ratio of suppression, and the steroid profile by liquid chromatography-tandem mass spectrometry were collected. The excised glands were processed entirely and histologically evaluated for the presence of glomerulosa hyperplasia, pattern (normal/micronodular/macronodular) and cellularity (foamy clear/ eosinophilic cells) of the cortex, metaplastic changes and pigment, size of the lesion/largest nodule, and vascular changes. Results: The patients (10 female/13 male) aged 32-72 years (average 48.23) at excision, and the biochemistry revealed hypokalemia (2.2-3.9mEq, average 3.4mEq), increased aldosterone (402-5960 pmol/L, mean 1463) and incomplete saline suppression test (1-33%, suppression, mean 15%). The glands weighed 7-51 g (average 20.28g) and the lesion/dominant nodule measured 3-29mm (average 17.42mm). Histologically, the glands revealed cortical adenomas (3 of clear cells and 3 of eosinophilic cells), macronodular cortical hyperplasia (5 clear cells and three mixed), and micronodular cortical hyperplasia (7 clear cells, two mixed). Diffuse glomerulosa hyperplasia and a hyaline arteriolosclerosis were observed in all cases, and adrenal medullary hyperplasia featured in 3 cases. The significant biochemical-morphological direct correlations were revealed for 11-deoxycortisol with myelolipomatous metaplasia and nodules &gt;2.0, and deoxycorticosterone with eosinophilic cells and cortical adenoma. Inverse correlations were observed for 18-hydroxy-corticosterone with clear cells, and micronodular cortex, deoxycorticosterone with clear cells, micronodular cortex and lesions &gt;2.0cm, and 17-hydroxyprogesterone with lesions &gt;2.0cm. Conclusions: PA is mainly for hyperplastic cortical lesions despite the clinical evidence for unilateral processes. A biochemical evaluation by mass spectrometry can identify mixed hypersecretion that correlates with less suppression to saline overload test, lower aldosterone/cortisol ratio, and hyperplastic glands with clear cell micronodular pattern and nodules&gt;2cm.