High aldosterone levels in the renal capsular vein from the left aldosterone-producing adenoma on adrenal venous sampling

Background

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is more frequently associated with cerebrovascular, cardiovascular, and chronic kidney diseases than essential hypertension. Conventional adrenal venous sampling (cAVS) in bilateral adrenal veins is the standard method for subtyping unilateral lesions, which are mostly aldosterone-producing adenoma (APA) and can be surgically treated, and bilateral lesions, which can be pharmacologically treated (1). However, some APAs are overlooked, where unilateral APA is incorrectly diagnosed as bilateral PA by cAVS. The APA blood flowing out through alternative drainage pathways other than the adrenal vein is one of the causes (2, 3).

Abundant venous networks are formed around the adrenal gland (4). Adrenal venography frequently demonstrates the connection of the adrenal vein with collateral blood channels. Adrenal blood, including APA blood, could drain via this channel; however, only a few reports of sampling in them and demonstrating elevated aldosterone levels are available (2, 5). Herein, we report a patient with PA who underwent AVS with a markedly high aldosterone concentration in the additional sampling of the left renal capsular vein connecting to the left adrenal nodule, which confirmed the diagnosis of left APA. Our case highlights the possibility of aberrant venous drainage in some APAs and the usefulness of sampling in the alternative drainage veins.

Case presentation

A 42-year-old female patient with no medical history experienced headaches and was diagnosed with hypertension (190/130 mmHg) and hypokalemia (serum potassium level of 3.1 mEq/L) at a local doctor. The PA screening test was positive, and she was referred to our hospital for further examination. On admission, her blood pressure was 111/76 mmHg, heart rate was 82 beats/min, and serum potassium level was 3.7 mEq/L and was taking amlodipine 10 mg and potassium chloride 3600 mg daily.

Investigation

Laboratory data revealed a high plasma aldosterone concentration (PAC; 321.8 pg/mL, normal range (NR): 4.0–82.1 pg/mL), low plasma renin activity (0.3 ng/mL/h, NR: 0.2–2.7 ng/mL/h), and high aldosterone-to-renin ratio (ARR; 1073, PA screening positive: ARR ≥ 200 and PAC ≥ 60 pg/mL). PA was hence confirmed with ARR of 703 (positive: ≥200) after 90 min of the captopril challenge test and PAC of 287.7 pg/mL (positive: ≥60 pg/mL) after 240 min of saline infusion test (1). A 1-mg dexamethasone suppression test revealed a negative subclinical Cushing’s syndrome with a low cortisol level.

Pre-contrast and dynamic contrast-enhanced computed tomography (CT) images with a 1-mm slice thickness revealed a 13-mm low-density nodule on the left adrenal gland and the adrenal vein anatomy (Fig. 1). Additionally, a fine venous connection between a left adrenal nodule and prominent renal capsular vein running nearby was depicted.

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A contrast-enhanced computed tomography image of the left adrenal gland (A) and three-dimensional reconstruction (B). The left adrenal nodule (arrow) is located in the lateral segment and the prominent renal capsular veins (arrowhead) running nearby.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 3; 10.1530/EDM-23-0041

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Adrenocorticotropic hormone (ACTH)-stimulated segmental AVS (sAVS), which is a sampling in bilateral adrenal central veins and the adrenal tributaries, was performed to localize the aldosterone excess as previously described (6, 7). The adrenal nodule was estimated to be located in the left lateral segment based on CT images (Fig. 1B). The venograms from the left adrenal vein and lateral tributary with a microcatheter revealed venous drainage to the renal capsular vein on AVS (Fig. 2A and B). sAVS can diagnose, but rarely overlooked, APAs, which were overlooked by cAVS (3, 6, 7). Therefore, the additional left renal capsular vein sampling was attempted to avoid such a situation. Sampling was feasible in the thin branch connected to the capsular vein although impossible in the prominent renal capsular vein (Fig. 2C).

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Venogram of the left adrenal central vein (A), the lateral tributary (B), and the renal capsular vein (C), and the schema of the left sampling sites and results (D). Black arrowheads with letters indicate sampling points (a: adrenal central vein, b–d: tributaries, and e: renal capsular vein) after adrenocorticotropic hormone (ACTH) stimulation, which correspond to those shown in Table 1. The lateral tributary is thought to be the nodule drainer referring to the computed tomography images. The venograms from the lateral tributary with a microcatheter revealed fine venous drainage to the renal capsular vein (black arrows). Sampling in the prominent renal capsular vein (white arrowhead) was not feasible probably because of poor blood flow, and it was possible in its fine branch. Sampling points after ACTH stimulation are also indicated by white arrows with aldosterone-to-cortisol ratio.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 3; 10.1530/EDM-23-0041

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Table 1 and Fig. 2D show the blood sampling results. The lateralization index (LI) for the adrenal central vein (defined as the ratio of aldosterone to cortisol on the dominant side over the contralateral side) was 36.1 and 48.3 before and after ACTH stimulation, respectively, which indicated a unilateral aldosterone excess from the left adrenal gland based on cAVS (1). The left lateral tributary blood revealed high PAC (66 700 pg/mL) and aldosterone-to-cortisol (A/C; 86.8 pg/mL per µg/dL), which corresponded to the nodular location, whereas other tributary samples revealed lower PAC and A/C (8). Furthermore, the left renal capsular vein blood revealed exceedingly higher PAC (224 000 pg/mL) and A/C (1493 pg/mL per µg/dL) than the left adrenal central vein (PAC: 45 000 pg/mL; A/C: 72.5 pg/mL per µg/dL) and tributaries, and the APA blood outflow was thought as the cause. Therefore, the sAVS diagnosis was a left unilateral aldosterone hypersecretion caused by an APA and left renal capsular vein sampling strongly confirmed the diagnosis.

Treatment

The patient subsequently underwent laparoscopic left partial adrenalectomy (9). Histopathological analysis revealed an aldosterone synthase (CYP11B2)-positive and clear cell-dominant adrenocortical adenoma, consistent with APA.

Outcome and follow-up

The patient’s hypertension, hypokalemia, and hyperaldosteronism were all resolved postoperatively. Complete clinical and biochemical success was achieved after 6 months with a blood pressure of 110/70 mmHg, serum potassium of 3.6 mEq/L, PAC of 13.8 pg/mL, PRA of 3.8 ng/mL/h, and ARR of 3.6 without medication (10).

Discussion

The left renal capsular vein, which we usually do not sample, was deemed to be connected to the left adrenal nodule and sampled in the present case during sAVS, which revealed a markedly high aldosterone level. This confirmed the diagnosis of left APA, highlighting the possibility of aberrant venous drainage in some APAs and the usefulness of sampling in the alternative drainage veins. A little direct evidence was reported on high aldosterone from APAs to the alternative drainage veins; hence, this report is valuable.

Some APAs are frequently overlooked by cAVS (2, 3, 9), as 26% of CYP11B2-positive APAs, which were diagnosed by sAVS, could not be localized by cAVS using LI of >4 after ACTH stimulation (7). Variant APA blood drainage is one of the causes of these overlooks in cAVS. However, few reports have demonstrated this drainage by sampling in them, such as the lumbar vein and inferior phrenic vein (2, 5). Adrenal venogram often depicts the venous connections to the renal capsular vein. To our knowledge, no report proved a much higher aldosterone level from the APA in the renal capsular vein than in the adrenal central veins and even tributaries.

The possibility of overlooking APA by alternative venous drainage was a concern in this case because the renal capsular vein was connected with the adrenal nodule on the preprocedural CT. sAVS, which is a sampling of the adrenal central veins and adrenal tributaries, can often prevent this overlooking, but it also rarely overlooks APA, similar to cAVS. Therefore, the renal capsular vein sampling was performed in the initial sAVS, which revealed a high aldosterone concentration, thereby increasing our confidence in diagnosing a left APA. However, high LI in the adrenal central veins and localized elevated aldosterone in tributaries could diagnose left unilateral PA for an APA, indicating a limited impact of alternative drainage sampling on the treatment strategy. Blood sampling in them is not always indispensable if alternative drainage of APA blood is strongly suspected. Referring to previous reports (2, 3), blood sampling in alternative drainage pathways at the repetitive AVS may be considered if the A/C in the bilateral adrenal veins is lower than that in the peripheral veins at the first cAVS (so-called apparent bilateral aldosterone suppression, or double-down) and APA is strongly suspected.

The collateral blood channels of the adrenal vein connect to the inferior phrenic vein on the left side, the renal capsular vein, and the lumbar vein. Sampling in the inferior phrenic vein connected to the adrenal vein is technically easy, but not the other veins due to their anatomical variations and often thinness. Blood cannot be sometimes collected although they are depicted thickly probably because of poor blood flow. Thus, the benefits for the diagnosis and the added technical difficulties, procedure time, and radiation exposure should be considered during blood sampling. There are no reports regarding these disadvantages of blood sampling from collateral blood channels. However, for sAVS, there are some reports regarding technical difficulties, time, radiation exposure, costs, and contrast load compared with cAVS (6, 11, 12, 13). To acquire the procedure of sAVS, even experienced angiographers need training with learning curve (12, 13). sAVS take longer time than cAVS, although sAVS are reported to be performed within a reasonable time (58–130 min) by highly skilled angiographers (6). It has been reported that the average radiation dose of sAVS was 838.7 mGy (range: 85.7–2557.2 mGy) and no patients experienced any complications related to radiation exposure, such as skin rash or ulceration (12). sAVS costs more than four times of cAVS, since the microcatheter is much more expensive than the conventional catheter (6, 11). In addition, sAVS require more contrast media than cAVS (11). Considering these points, it is important to select patients who would derive clinical benefits from sAVS instead of cAVS.

In conclusion, we revealed direct evidence of APA blood venous drainage into the renal capsular vein. Sampling from an alternative drainage pathway could be beneficial for APA diagnosis if venous drainage of APA blood is assumed.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This research was supported by JSPS KAKENHI grant number 23K14831.

Patient consent

Written informed consent has been obtained from the patient for the publication of clinical details and clinical image.

Author contribution statement

RH conceived of the study and wrote the manuscript with support from HT, KN, KM, and SM. HT and JS supervised the project. All authors have read and approved the final manuscript.