11-Deoxycorticosterone Producing Adrenal Hyperplasia as a Very Unusual Cause of Endocrine Hypertension: Case Report and Systematic Review of the Literature

Abstract

Background and objectives: 11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of.

Design and methods: We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021.

Results: We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions.

Conclusions: 11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable.

Systematic review registration: Open Science Framework, 10.17605/OSF.IO/NR7UV.

Keywords: 11-deoxycorticosterone (DOC); DOC-producing adrenal tumor; adrenal adenoma; adrenal hyperplasia; adrenocortical carcinoma; mineralocorticoid excess; mineralocorticoid hypertension.

Figure 1

Macroscopic image of the excised adrenal gland (6 × 2 × 2 cm) with a visible multi-nodular pattern. The larger nodule was round, measured 12 mm in diameter and was composed by a bright-yellow soft tissue. Other less defined nodules were found.

Figure 2

Microscopic images of the left adrenal gland. (A) Panoramic microscopic image of the larger nodule (Hematoxylin–Eosin; magnification ×4). Lack of capsule and fear delimitation of the normal cortex (arrows). (B) Representative histologic section of the adenomatous left adrenal hyperplasia, showing two types of cell population. No atypia, mitosis or necrosis was detected (Hematoxylin–Eosin; magnification ×20). (C) Positive Ki-67 immunohistochemical staining in less than 1% of adrenal cells (magnification ×20).

Figure 3

Immunohistochemical analysis of steroidogenic enzymes. (A) Sparse expression of CYP11B2 immunoreactivity in the zona glomerulosa. Only two clusters of ALD-producing cells stained (arrows) in the outer margin of the subcapsular zona glomerulosa (magnification ×4). (B) Normal expression of CYP11B1 in the zona fasciculata (magnification ×4).

Figure 4

Steroid hormone metabolism pathways. (−) and (+) represent diminished and increased enzyme activity respectively detected during intratumoral analysis of steroidogenic enzymes of nine case reports (including ours). 3β-HSD, 3β-hydroxysteroid dehydrogenase; 18-OH-corticosterone, 18-hydroxy-corticosterone; 17-OH-pregnenolone, 17-hydroxy-pregnenolone; 17-OH-progesterone, 17-hydroxy-progesterone, 17β-HSD, 17β-hydroxysteroid dehydrogenase.

Figure 5

Flowchart of the literature review.

Figure 6

Algorithm for the diagnostic approach of patients with non-ALD-dependent mineralocorticoid hypertension. BP, blood pressure; ALD, aldosterone; PRA, plasma renin activity; DOC, 11-deoxycorticosterone; 19-Nor-DOC, 19-Nor-deoxycorticosterone; 18-OH-DOC, 18-hydroxy-deoxycorticosterone; CT, computed tomography; ACTH, adrenocorticotropic hormone.