Pearls & Oy-sters: Cerebral Microbleeds Caused by Adrenocortical Adenoma-Related Primary Aldosteronism

Pearls

• Multiple cerebral microbleeds (CMBs) increase in prevalence with age.

• Hypertension itself is not an independent factor for frequency of CMBs and workup should be performed in patients with age-advanced CMBs.

• Concomitant lobar and deep CMBs are caused by hypertensive small vessel disease rather than cerebral amyloid angiopathy (CAA).

• Primary aldosteronism (PA) can cause numerous concomitant lobar and deep CMBs in a relatively young population through oxidative stress caused by excessive aldosterone and direct injuries resulting from hypertension.

Oy-sters

• Secondary hypertension should be considered in hypertensive patients with numerous concomitant lobar and deep CMBs and unexplained retinal hemorrhage.

• PA could be among the differential diagnoses in hypertensive patients with concomitant lobar and deep CMBs with accompanying low serum potassium levels.

A 47-year-old man came to the outpatient neurology clinic at a university-affiliated hospital. He complained of word-finding difficulty and slurred speech, which had occurred abruptly with accompanying dizziness in the morning 17 days prior to the visit and had been improving since then. He was still working as a computer programmer. His past medical history was significant for hypertension (on 3 antihypertensive medications) over 7 years, a prior episode of transient vertigo with negative workup, and incidental retinal hemorrhages of unclear etiology. At his visit, his blood pressure (BP) was 145 mm Hg/95 mm Hg. On the NIH Stroke Scale (NIHSS), he was scored 1 due to mild transcortical motor aphasia. His brain MRI was taken on the same day as the appointment and revealed an acute 1.7-cm intracranial hemorrhage (ICH) in the left superior frontal lobe with ICH score of 0 (figure, A). The MRI showed >200 CMBs in the junctions of the white and gray matter, basal ganglia, pons, and cerebellum on gradient echo T2-weighted imaging (figure, B). In addition, 3 lacunes and white matter hyperintensities (Fazekas grade 2) were detected on T2-weighted imaging. He was instructed to keep taking his antihypertensive medications.

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Figure Brain MRI, Brain CT, ¹⁸F-Flutemetamol Amyloid PET Scan, Retinal Image, Adrenal CT, Adrenal Mass Specimen, and Histopathologic Section of Adrenocortical Adenoma in a Patient With Adrenocortical Adenoma Associated With Primary Aldosteronism

(A, B) Brain MRI. Gradient echo T2-weighted imaging shows an intracerebral hemorrhage (ICH) in the left superior frontal lobe and cerebral microbleeds (CMBs) in the Junction of white matter and gray matter, basal ganglia, and thalami. (C) An acute ICH in the left basal ganglia is seen in the brain CT. (D) ¹⁸F-flutemetamol amyloid PET showed no amyloid deposition in brain. (E) Retinal dotty hemorrhages (arrows) are shown. (F) Adrenal CT shows a 1.7-cm mass in the left adrenal gland (arrow). (G) The adrenal mass is 1.3 × 1.3 × 1.3 mL and well-defined. (H) Adrenocortical adenoma is pathologically confirmed, based on microscopic findings: well-defined cell borders, polygonal pink cells, clear cells that have abundant, finely vacuolated cytoplasm, and nuclei that are central, round, and bland (hematoxylin & eosin stating, at 400× magnification, bar = 50 μm).

On the following day, the patient visited the emergency department with sudden-onset right hemiparesis, which had occurred at midnight, 1 hour prior to his visit to the emergency department. His BP was 170/115 mm Hg. He was alert and attentive but showed right arm and leg weakness in addition to mild transcortical motor aphasia (3 on NIHSS). His brain CT scan showed a new acute ICH (0 on the ICH score) in the left basal ganglia (figure, C). He was admitted to the ward for conservative management of ICHs.

During the patient’s 10-day admission, his neurologic signs improved with only transcortical motor aphasia remained (1 on NIHSS), but his regimen was uptitrated to include a 4th antihypertensive medication. His blood test revealed low levels of serum potassium (3.5 mmol/L on the first day of admission, 3.0 mmol/L on the 4th day of admission [normal range 3.5–5.1 mmol/L]); however, he did not show related symptoms or signs. NOTCH3 gene test did not detect any pathogenic/likely pathogenic variants. His APOE genotype was ε2/ε3. ¹⁸F-flutemetamol amyloid PET was conducted to exclude the possibility of combined CAA. The results revealed no evidence of brain amyloid deposition (figure, D). At follow-up 3 weeks after discharge, 24-hour ambulatory BP monitoring showed that his systolic BP was 110–130 mm Hg. Therefore, his antihypertensive medications were altered to include 3 again. Three months after the onset of the second ICH, he returned to work.

Six months after the patient’s ICHs, a follow-up serum electrolyte test revealed low potassium levels (2.7 mmol/L). Therefore, he was recommended to stop taking the diuretic among his antihypertensive medications for 1 month. However, potassium levels were still low (2.8 mmol/L). He was supplemented with oral potassium chloride. After discontinuing the diuretic, his BP was 113/83 mm Hg. As a result, considering that he presented with numerous CMBs accompanied by 2 ICHs within an 18-day period, unexplained retinal hemorrhage (figure, E), and persistently low serum potassium, secondary hypertension was suspected. Subsequently, a hormonal test was conducted at 8 am, which revealed the following results (normal range within parentheses): serum aldosterone 30.31 ng/dL (supine position, 4.1–20.8 ng/dL) and plasma renin activity ≤0.20 ng/mL/h (0.5–1.9 ng/mL/h). The ratio of serum aldosterone (ng/dL) to plasma renin activity (ng/ml/h) was over 20, which indicated probable PA. A saline loading test was performed to confirm PA. After an IV injection of 2 L of normal saline for 4 hours, serum aldosterone level was 45.87 ng/dL and was not reduced to <5 ng/dL, which confirmed the PA. Adrenal CT (figure, F) showed a 1.7-cm mass in the left adrenal gland. The adrenal mass, removed by laparoscopic left adrenalectomy, was a 1.3×1.3×1.3 cm³, well-defined adrenocortical adenoma (figure, G and H). After surgical treatment, the patient’s BP was under control with only 1 antihypertensive medication. He was diagnosed with secondary hypertension due to adrenocortical adenoma–related PA.