Abstract
A 65-year-old male with systemic hypertension, progressively rising aldosterone levels, low plasma renin activity, contrast Magnetic resonance imaging (MRI) described left adrenal lesion isointense to liver parenchyma on T2-weighted images and other features suggestive of left adrenal incidentaloma underwent 68Ga-Pentixafor Positron emission tomography-computed tomography (PET/CT), which unexpectedly did not show tracer uptake in the known left adrenal adenoma. However, the said nodule showed significant focal tracer uptake on F-18 Fluorodeoxyglucose (FDG)-PET/CT that was done within 2 weeks of 68Ga-Pentixafor PET/CT study. This unusual finding, which has hitherto been unreported in known patients of primary aldosteronism needs further exploration to determine its clinical significance.
Keywords: 68Ga-Pentixafor positron emission tomography-computed tomography, adrenal adenoma, contrast magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography-computed tomography, primary aldosteronism
A 65-year-old male, a known case of type 2 diabetes mellitus, systemic hypertension, dilated cardiomyopathy, and Contrast enhanced computed tomography (CECT) diagnosed left adrenal incidentaloma was subjected to standard of care pharmacotherapy including mineralocorticoid receptor antagonist, beta blocker, diuretic, and angiotensin receptor blocker. Further evaluation revealed rising serum aldosterone from 536 pg/mL at the time of initial evaluation to 1203 pg/mL on the 11th day of admission with normal plasma renin activity (0.19 ng/ml/h). 68Ga-Pentixafor positron emission tomography-computed tomography (PET/CT) MIP [Figure 1a] and fused trans-axial image [Figure 1b] showed no tracer avidity in computed tomography delineated left adrenal gland nodule measuring 17 mm × 15 mm while corresponding 18F-fluorodeoxyglucose (18F-FDG) PET/CT trans-axial image [Figure 1d] and MIP [Figure 1e] revealed focal FDG uptake in the nodule (SUVma × 3.58). Contrast MRI [Figure 1c] showed adrenal lesion isointense to liver parenchyma on T2 weighted image and enhancement in venous phase with delayed washout, suggestive of left adrenal adenoma. The patient responded to pharmacotherapy for hypertension (combination of mineralocorticoid receptor antagonist, beta blocker, diuretics, and angiotensin receptor blocker) and remained under observation. He was asymptomatic for 1 year, no imaging/blood tests were done in this interval. After 1 year, his laboratory results showed normal aldosterone levels (16.4 pg/mL) with normal Plasma renin activity (PRA) (0.18 ng/ml/h) elevated plasma renin (89.21 uIU/ml), and normal Aldosterone/Direct Renin ratio.
Figure 1.

68Ga Pentixafor PET/ CT MIP (a) and fused trans axial image (b) showed no tracer avidity in computed tomography delineated left adrenal gland nodule measuring 17 mm × 15 mm while corresponding 18F-FDG-PET/CT trans axial image (d) and MIP (e) revealed focal FDG uptake in the nodule (SUVmax: 3.58). Contrast MRI (c) showed adrenal lesion isointense to liver parenchyma on T2 weighted image and enhancement in venous phase with delayed washout, suggestive of left adrenal adenoma
Conn syndrome or primary aldosteronism (PA) results from nonsuppressible aldosterone hypersecretion by the adrenal cortex with a classical presentation of hypertension and hypokalemia. Most common subtypes include unilateral aldosterone-producing adenomas (APA; >10 mm) or aldosterone-producing micronodules (<10 mm) and bilateral idiopathic hyperaldosteronism (IHA; bilateral adrenal hyperplasia). Differentiating these two conditions is imperative since the former needs surgical correction while the latter (IHA) requires medical management.[1,2,3,4,5] Adrenal venous sampling is the gold standard for definitive lateralization of aldosterone secretion but is invasive, technically challenging, and not widely available.[6] Robust expression of chemokine receptor type 4 (CXCR 4) in APA cells forms the basis for use of 68Ga-Pentixafor PET/CT molecular imaging as an effective noninvasive tool for visualizing aldosterone-producing tissues to subtype PA.[7,8,9,10,11,12,13,14]
In the study by Ding et al.,[9] a single 0.6-cm lesion had a false-negative Ga-68 Pentixafor PET result in a patient of aldosterone-producing adenoma (APA) causing primary hyperaldosteronism, while one patient presented with a false-negative APA lesion on adrenal vein sampling. The former was ascribed to the limitation of the technique for small lesions with reduced spatial resolution. False-positive 68Ga-pentixafor adrenal uptake was observed in idiopathic aldosterone hyperplasia or nonfunctioning adrenal adenomas.[9]
In the present case, the clinical and biochemical picture was suggestive of PA with MRI revealing an adrenal nodule. However, unexpectedly functional imaging showed negative 68Ga-Pentixafor PET/CT (indicative of negative CXCR4 expression) and positive F-18 FDG-PET/CT (suggestive of Glucose transporter (GLUT) expression) scans. The cause and significance of this hitherto unreported finding are not reported in the literature. Nevertheless, such patients need to be kept under surveillance as shown in this patient, in whom the ancillary biochemical findings normalized after 1 year.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
References
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