A Hidden Culprit: Aldosteronoma as a Rare Cause of Refractory Hypertension in Autosomal‐Dominant Polycystic Kidney Disease

ABSTRACT

Hypertension is common in autosomal‐dominant polycystic kidney disease (ADPKD) but may occasionally reflect a secondary etiology. We report a 71‐year‐old man with ADPKD and end‐stage renal disease who developed persistent, refractory hypertension following renal transplantation despite multidrug therapy and bilateral native nephrectomy. Evaluation revealed an elevated aldosterone‐to‐renin ratio, and adrenal venous sampling confirmed unilateral aldosterone excess consistent with a left aldosterone‐producing adenoma. The patient underwent robotic adrenalectomy with subsequent improvement in blood pressure control and reduced antihypertensive requirements. This case highlights the importance of evaluating for primary hyperaldosteronism in patients with ADPKD and resistant hypertension, even in the setting of advanced renal disease or prior nephrectomy.

Key Clinical Message

In patients with autosomal‐dominant polycystic kidney disease and resistant hypertension, secondary causes, such as primary hyperaldosteronism or aldosteronoma, should be considered. Early recognition and targeted treatment can improve outcomes, even in complex transplant and status post bilateral nephrectomy patients.

Abbreviations

ACE

angiotensin‐converting enzyme

ADPKD

autosomal‐dominant polycystic kidney disease

ARBs

angiotensin receptor blockers

ARR

aldosterone‐to‐renin ratio

CMV

cytomegalovirus

CT

Computed tomography

ESRD

end‐stage renal disease

HTN

Hypertension

MRI

magnetic resonance imaging

RAS

renin‐angiotensin system

1. Introduction

Hypertension (HTN) is one of the most common features of autosomal‐dominant polycystic kidney disease (ADPKD) and often presents before there is any discernible decline in renal function [1, 2]. While the pathogenesis of HTN in ADPKD is not fully understood, it is believed to be related to the increased activity of the renin‐angiotensin system (RAS) due to cyst expansion [1, 2]. For this reason, angiotensin‐converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are the first‐line agents for treating HTN in ADPKD [3].

Aldosterone‐producing adrenal adenomas, or aldosteronomas, are rare neuroendocrine tumors present in up to 1%–2% of patients with HTN [4]. Their continuous release of the aldosterone contributes to persistent HTN [4, 5, 6]. Aldosteronomas can mimic some of the hypertensive features of ADPKD, while remaining refractory to the effects of anti‐hypertensive medications [5, 7, 8, 9, 10].

The coexistence of aldosteronoma in ADPKD is exceedingly rare. This case study describes a patient with ADPKD who developed refractory hypertension and was ultimately diagnosed with an aldosteronoma. We describe the patient's work up, diagnosis, treatment, and recovery following adrenalectomy.

2. Case Presentation

2.1. Case History/Examination

The patient is a 71‐year‐old Caucasian male who initially presented to our department for evaluation for renal transplantation in April 2023. He had a long‐standing history of HTN and ADPKD diagnosed in 2010, with progression to end‐stage renal disease (ESRD) in 2022. Family history was significant for ADPKD in multiple relatives, including his mother, two brothers, a maternal uncle, and a maternal aunt. There was no known family history of endocrine disorders or adrenal tumors. Prior to evaluation, he had been dialyzing at home using peritoneal dialysis for 13 months. During this time, he was not taking any antihypertensive medications.

He underwent successful renal transplantation in May 2023. Post‐operatively, the patient had slow but primary graft function, produced good urine output, and did not require dialysis. However, in the year following his transplant, the patient developed chronic allograft dysfunction, complicated by BK polyoma virus and cytomegalovirus (CMV) viremia. He subsequently developed refractory HTN requiring multiple hospital admissions for hypertensive emergencies. His antihypertensive regimen was highly dynamic, with medications frequently adjusted on a daily to weekly basis. Over the course of treatment, he received agents from all major antihypertensive classes, including beta‐blockers, calcium channel blockers, renin–angiotensin system inhibitors, mineralocorticoid receptor antagonists, thiazide and loop diuretics, central alpha‐agonists, and direct vasodilators. Despite maximal tolerated multi‐class therapy, blood pressure remained poorly controlled.

In April 2024, he underwent bilateral native nephrectomy in an effort to improve blood pressure control and manage worsening BK nephropathy; however, hypertension persisted despite this intervention.

2.2. Differential Diagnosis, Investigations and Treatment

Throughout this time, the patient had undergone workup for secondary causes of HTN. Notably, the patient was found to have an elevated aldosterone‐to‐renin ratio (ARR) of 36 (normal < 30) [11] suggestive of primary hyperaldosteronism. At the time of testing, the patient remained on multiple antihypertensive medications, including clonidine, carvedilol, nifedipine, hydralazine, bumetanide, and doxazosin. No mineralocorticoid receptor antagonists were being administered. Medication washout was not feasible due to severe uncontrolled HTN.

The patient then underwent adrenal venous sampling (AVS). Aldosterone levels were 12.8 ng/dL in the right adrenal vein and 60.5 ng/dL in the left adrenal vein. Peripheral reference samples obtained from the inferior vena cava demonstrated aldosterone levels of 11.2 ng/dL (high IVC) and 11.8 ng/dL (low IVC). Cortisol measurements were not obtained at the time of the procedure. However, the marked elevation in left adrenal vein aldosterone relative to the right adrenal vein and peripheral samples was interpreted clinically as consistent with left‐sided aldosterone excess.

The patient subsequently underwent a robotic left adrenalectomy. Final pathology demonstrated a 0.6 cm well‐circumscribed adrenal adenoma. The tumor was confined to the adrenal cortex without evidence of vascular or capsular invasion, and the surgical margins were negative. Histological evaluation demonstrated no high nuclear grade, increased mitotic activity, atypical mitoses, or necrosis. These findings were consistent with a benign adrenal adenoma; therefore, no formal oncologic stage was assigned. The prognosis is favorable, with a low risk of recurrence and high rates of HTN improvement or resolution following surgical resection [11, 12, 13].

2.3. Conclusion and Results

Post‐operatively, the patient's blood pressure remained well controlled with low‐dose bumetanide and carvedilol for 6 months. The patient was then re‐approved by the transplant committee for kidney transplantation and underwent successful renal transplantation 1 month later.

3. Discussion

Aldosteronoma is a rare neuroendocrine tumor that occurs in the adrenal glands. It can present in a variety of ways, most common being hypertension and low potassium [5, 9]. It is assumed to cause around 1%–2% of hypertension cases and around 8% of normokalemic hypertensive cases [4, 5, 9, 14]. This tumor is one of the major causes of primary hyperaldosteronism, occurring at a rate of around 30% [5]. Some studies have claimed that this tumor is a more common cause of hypertension than previously thought [5]. Likewise, the incidence of ADPKD is estimated to be one in 1000, making the combination of these two conditions substantially unlikely [14].

Due to the low potassium, patients experience a number of symptoms such as weakness, paresthesia, tetany, cramping, and polyuria [5, 9]. Other lab findings include metabolic alkalosis, elevated aldosterone level (urine and serum), and elevated plasma aldosterone‐to‐renin ratio, the latter being very commonly used for diagnosis [5]. Cross‐sectional imaging with computed tomography (CT) is recommended for initial evaluation of adrenal anatomy and to exclude large or potentially malignant lesions; however, it cannot reliably lateralize or distinguish nonfunctioning incidentalomas from aldosterone‐producing adenomas [11]. Adrenal venous sampling (AVS) is considered the gold standard for distinguishing unilateral from bilateral primary hyperaldosteronism and for guiding subsequent management [11, 15].

Treatment of these tumors involve either medications or a surgical approach [4, 5, 6]. Surgery is indicated if the tumor is unilateral, while it is contraindicated if any bilateral tumors are present [16]. Surgery is usually done through a laparoscopic approach, with adrenalectomy being the procedure of choice, although studies have shown that around 33% of patients still have persistent hypertension post‐op [5, 6]. In these cases, symptoms are managed with medication. If surgery is not an option, then medications such as spironolactone (aldosterone antagonist) or amiloride (potassium sparing diuretic) can be used to treat associated symptoms. ACE inhibitors and calcium channel blockers can also be used to manage hypertension [16].

This case is unique because it describes an aldosteronoma in the context of ADPKD, which is already an uncommon finding and not typically known to be associated with aldosteronomas [10]. Additionally, this patient presented with two causes of secondary HTN creating unforeseen challenges in arriving at the proper diagnosis [16]. As such, the hypertensive etiology from the aldosteronoma was masked by the history of ADPKD [10]. This case also highlights an important physiologic consideration regarding the extra‐renal effects of aldosterone. Although its classic hypertensive effects are mediated through renal sodium retention, aldosterone also increases systemic vascular resistance through effects on vascular tone, remodeling, and arterial stiffness [17, 18]. These mechanisms likely explain the persistence of HTN in our patient.

Published literature describing ADPKD with concomitant aldosteronoma is sparse. Two case reports published in 1994 have described this phenomenon [9, 10, 11, 14]. Loiu et al. described three young patients with both conditions. Two of these patients were female and one was male. Gejyo et al. described a similar middle‐aged female [14, 19]. An additional case report published in 2018 by Mital et al. described a similar case in a young adult woman following pregnancy [7]. Given the low incidence of these conditions overlapping, physicians with an elevated index of suspicion for the superimposition of these conditions may be more likely to quickly and accurately diagnose the phenomenon, improving patient morbidity and quality of life. To our knowledge, this makes the current paper the only reported case of an older male patient with ADPKD and a concomitant aldosteronoma.

The coexistence of ADPKD and primary aldosteronism in this patient is not well understood, and no established pathogenic association between these conditions has been reported. Although ADPKD is characterized by HTN mediated in part by chronic activation of the RAS [1, 2], a mechanistic link between this pathway and the development of aldosterone‐producing adenomas has not been established. The concurrence of these conditions is therefore most likely coincidental. However, given the high prevalence of hypertension in ADPKD, secondary causes such as primary aldosteronism may be underrecognized when elevated blood pressure is attributed solely to underlying renal disease.

This case has several limitations. As a single‐patient report, the findings may not be generalizable. The patient's history of ADPKD, renal transplantation, chronic allograft dysfunction, and prior bilateral nephrectomy introduced multiple potential contributors to elevated blood pressure that may have delayed recognition of primary hyperaldosteronism. Additionally, long‐term biochemical and clinical follow‐up after adrenalectomy was limited. Complete normalization of aldosterone–renin parameters following surgery was not consistently documented. Furthermore, the retrospective nature of this report limits the ability to fully assess the temporal relationship between clinical interventions and blood pressure improvement.

Author Contributions

Matthew Wainstein: conceptualization, investigation, project administration, writing – original draft, writing – review and editing. Maya Mendonsa: conceptualization, investigation, writing – original draft, writing – review and editing. Matthew Folkman: conceptualization, investigation, writing – original draft, writing – review and editing. Ajay Nair: conceptualization, investigation, writing – original draft, writing – review and editing. Samuel Simpson: conceptualization, investigation, writing – original draft, writing – review and editing. Kaelee Storey: conceptualization, investigation, writing – original draft, writing – review and editing. Brandon Mount: conceptualization, investigation, writing – original draft, writing – review and editing. Obi Ekwenna: conceptualization, investigation, supervision, writing – original draft, writing – review and editing.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.

Consent

Written informed consent was obtained from the patient for publication of this case report.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

Data sharing not applicable‐no new data generated, or the article describes entirely theoretical research.