Conn syndrome, formally called primary aldosteronism, is a condition in which one or both adrenal glands pump out far too much of the hormone aldosterone, driving up blood pressure and depleting potassium. Once considered rare, it is now recognized as one of the most common treatable causes of hypertension, potentially affecting more than one in five people with hard-to-control blood pressure. The name comes from Jerome Conn, the endocrinologist who first described a single adrenal tumor causing the problem in 1955, but the condition is broader and more nuanced than a single tumor on a single gland.
What Aldosterone Does and Why Too Much Is a Problem
Aldosterone is a hormone produced in the outer layer of the adrenal glands. Its main job is to tell your kidneys to hold on to sodium and water while releasing potassium. In healthy people, this system keeps blood pressure and electrolytes in balance. When aldosterone production goes haywire and stays elevated regardless of the body’s actual needs, the kidneys retain too much sodium and fluid, blood volume rises, and blood pressure climbs. Meanwhile, potassium gets flushed out, which can cause muscle weakness, cramping, and heart rhythm disturbances.
The condition comes in two main forms. In roughly a third of cases, a small benign tumor on one adrenal gland, called an aldosterone-producing adenoma, is the culprit. In the majority of cases, both adrenal glands are overactive, a pattern called bilateral adrenal hyperplasia. A handful of rarer subtypes exist, including unilateral hyperplasia and, very occasionally, adrenal cancer, but these are uncommon. The distinction between a one-sided tumor and two overactive glands matters enormously because it determines whether surgery is an option.
Far More Common Than Doctors Used to Think
For decades, textbooks described Conn syndrome as an uncommon curiosity, found in fewer than 1% of people with high blood pressure. That estimate has been dramatically revised. A large cross-sectional study using mass spectrometry-based hormone measurements found that biochemically overt primary aldosteronism was present in roughly 16% of people with stage 1 hypertension, about 22% of those with stage 2 hypertension, and 22% of those with resistant hypertension (blood pressure that stays high despite three or more medications).1PubMed Central. The Unrecognized Prevalence of Primary Aldosteronism: A Cross-sectional Study An earlier 20-year retrospective study of over 1,600 patients with resistant hypertension found primary aldosteronism in about 11%.2PubMed. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study
The numbers vary depending on how aggressively researchers screen and which population they study, but the consensus now is that primary aldosteronism has been massively underdiagnosed. A large part of the problem is that doctors often only suspect it when potassium is low, and low potassium turns out to be absent in many patients. In one German registry of over 550 patients with confirmed primary aldosteronism, only about 56% had low potassium.3The Journal of Clinical Endocrinology & Metabolism. Cardiovascular and Cerebrovascular Comorbidities of Hypokalemic and Normokalemic Primary Aldosteronism: Results of the German Conn’s Registry In the large resistant-hypertension cohort, the figure was even lower, at about 46%.4PubMed. Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study Waiting for potassium to drop before investigating means missing roughly half of all cases.
Damage That Goes Beyond High Blood Pressure
If Conn syndrome were simply another route to elevated blood pressure, treating it would be straightforward: lower the pressure by any means and move on. But excess aldosterone does direct harm to the heart, blood vessels, and kidneys independent of blood pressure itself. Animal and human studies have shown that sustained high aldosterone levels cause fibrosis of the heart muscle. Patients with primary aldosteronism show more myocardial fibrosis on echocardiography than patients with ordinary high blood pressure at similar levels.5American Journal of Hypertension. Aldosterone-induced cardiac damage: focus on blood pressure independent effects This fibrosis stiffens the heart and raises the risk of heart failure and arrhythmias.
The metabolic fallout is also significant. Aldosterone impairs insulin sensitivity in fat and muscle tissue, partly by depleting potassium, partly by ramping up inflammatory signaling, and partly by suppressing adiponectin, a protective hormone produced by fat cells.6PubMed Central. Effects of aldosterone on insulin sensitivity and secretion This means people with Conn syndrome are at higher risk for glucose intolerance and type 2 diabetes on top of their cardiovascular burden. The kidneys take a hit too, with chronic excess aldosterone promoting kidney scarring and accelerating the decline in kidney function over time.
How the Diagnosis Works
Screening for Conn syndrome starts with a blood test: the aldosterone-to-renin ratio, or ARR. The idea is simple. In primary aldosteronism, aldosterone is high while renin (the enzyme the kidneys release to stimulate aldosterone) is suppressed, because the adrenal gland is acting on its own. A high ratio flags possible disease. The trouble is that blood pressure medications can throw the ratio off. Beta-blockers can push the ratio artificially high, creating false positives, while certain other drugs, particularly angiotensin receptor blockers, can suppress it enough to cause false negatives.7PubMed. Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism A critical review of the literature confirmed that many commonly prescribed antihypertensives affect the ARR, though the magnitude of these effects is poorly quantified.8PubMed Central. The effect of medication on the aldosterone-to-renin ratio. A critical review of the literature
Because of this interference, specialists often ask patients to switch to medications that have less impact on the ratio, such as doxazosin or certain calcium-channel blockers, before screening. That alone can be a logistical headache, especially for people whose blood pressure is dangerously high and hard to control with limited drug options.
A positive screening ratio does not clinch the diagnosis. Guidelines recommend a confirmatory test to prove that aldosterone production is truly autonomous and does not suppress the way it should. The most common options are the saline infusion test, in which the patient receives intravenous salt water over several hours, and the captopril challenge test, in which the patient takes a dose of an ACE inhibitor and aldosterone is measured before and after.9PubMed Central. Performance of Confirmatory Tests for Diagnosing Primary Aldosteronism: a Systematic Review and Meta-Analysis A study in Chinese patients comparing both found the saline infusion test slightly outperformed the captopril challenge in terms of sensitivity and specificity at optimal cutoffs.10The Journal of Clinical Endocrinology & Metabolism. Evaluation of the Saline Infusion Test and the Captopril Challenge Test in Chinese Patients With Primary Aldosteronism Neither test is perfect, and the choice often depends on local expertise and patient safety considerations.
Telling One Side From Two
Once primary aldosteronism is confirmed, the next step is figuring out whether the problem is coming from one adrenal gland or both. This is the single most important fork in the clinical road. A one-sided source can potentially be cured by removing that adrenal gland. Bilateral disease is managed with medication long-term.
CT scans seem like the obvious tool, but they are surprisingly unreliable here. A direct comparison found that CT imaging was either inaccurate or added no useful information in about 68% of patients with confirmed primary aldosteronism.11PubMed. Comparison of adrenal vein sampling and computed tomography in the differentiation of primary aldosteronism CT can miss tiny adenomas, mistake a nonfunctioning lump for the culprit, or fail to recognize bilateral hyperplasia when the glands look normal-sized. A separate study measuring adrenal gland dimensions on CT found that limb width measurements could reliably identify bilateral hyperplasia, with sensitivity and specificity reaching 100% at specific thresholds, but this works only for detecting enlarged glands, not for confirming which gland is producing aldosterone.12AJR Am J Roentgenol. CT of primary hyperaldosteronism (Conn’s syndrome): the value of measuring the adrenal gland
The gold standard remains adrenal vein sampling (AVS), an invasive procedure where a radiologist threads catheters into the tiny veins draining each adrenal gland and measures aldosterone directly. It gives the clearest picture of which side is overproducing but requires considerable technical skill. Some centers report failure rates as high as 20-30% due to difficulty cannulating the right adrenal vein.
A promising alternative is a molecular imaging scan using a radiotracer called [11C]metomidate, which binds to the enzymes in adrenal tissue that make aldosterone. A prospective trial of 143 patients found that this PET-CT scan was noninferior to adrenal vein sampling for predicting biochemical remission after surgery, with accuracy around 73% compared with 64% for AVS.13PubMed Central. [(11)C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial A smaller pilot study found that combining PET-CT with AVS caught more cases of unilateral disease than either test alone, because each sometimes identified cases the other missed.14PubMed. 11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial This scan is not yet widely available but could eventually spare many patients the discomfort of catheter-based sampling.
Surgery for One-Sided Disease
When adrenal vein sampling or equivalent testing confirms that one gland is the problem, laparoscopic adrenalectomy (keyhole removal of the gland) is the treatment of choice. The surgery is typically straightforward and corrects the electrolyte problems reliably. In one study, both low potassium and high sodium resolved in every patient who underwent surgery.15PubMed Central. Short- and long-term results of laparoscopic adrenalectomy for Conn’s syndrome
Blood pressure is a different story. Cure of hypertension, meaning normal blood pressure with no medications, happens in a minority of cases. A large international study of 435 patients who had unilateral adrenalectomy found that about 27% achieved complete cure, another 31% had clear improvement (lower pressure or fewer medications), and roughly 42% had no clear success, though even within that last group blood pressure still dropped and the average number of medications went down.16JAMA Surgery. Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism Older age, longer duration of hypertension before surgery, and having more severe disease all predict a lower chance of achieving medication-free blood pressure after surgery. That said, the benefits extend beyond blood pressure control. A meta-analysis found that surgery was associated with a substantially lower risk of death and major cardiovascular events compared with long-term medication alone, with a hazard ratio for death of about 0.34.17PubMed Central. Time to Benefit of Surgery vs Targeted Medical Therapy for Patients With Primary Aldosteronism: A Meta-analysis Surgery also reduced the risk of hospitalization for heart failure and progression to chronic kidney disease. In absolute terms, treating 200 patients surgically instead of medically would prevent one death after about a year.
Medical Treatment for Bilateral Disease
When both glands are overactive, or when surgery is not feasible, the mainstay treatment is a class of drugs called mineralocorticoid receptor antagonists (MRAs). Spironolactone is the oldest and best-studied option. It blocks the receptor that aldosterone activates, effectively shielding the kidneys and heart from the hormone’s effects. Eplerenone is a newer alternative that targets the same receptor more selectively. In a head-to-head trial of 17 patients per group, both drugs normalized blood pressure in roughly 77-82% of patients, and both restored potassium levels within four weeks.18PubMed. Spironolactone versus eplerenone for the treatment of idiopathic hyperaldosteronism
The practical difference between the two lies in side effects. Spironolactone is not purely selective for the mineralocorticoid receptor; it also cross-reacts with androgen and progesterone receptors, which means it can cause breast tenderness and breast enlargement in men (gynecomastia). A larger double-blind study confirmed that spironolactone lowered diastolic blood pressure more effectively than eplerenone but also caused significantly more gynecomastia in men (about 21% vs 5%) and breast pain in women (about 21% vs 0%).19Journal of Hypertension. A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism For people who tolerate spironolactone without sexual side effects, it remains a first-line choice because it tends to be more potent and far cheaper. Eplerenone is a reasonable alternative when those side effects become intolerable.
Both drugs carry a risk of raising potassium too high, especially in patients with impaired kidney function, so regular blood monitoring is essential in the early months of treatment.
The Genetic Angle
Most cases of Conn syndrome are sporadic, meaning they arise without an inherited predisposition. In aldosterone-producing adenomas, researchers have identified somatic mutations (mutations that occur in the tumor cells but are not inherited) in more than 90% of cases. These mutations typically hit genes encoding ion channels and pumps that regulate cell signaling in the adrenal gland.20PubMed Central. Genetics of Primary Aldosteronism The most frequently mutated gene is KCNJ5, which encodes a potassium channel; mutations in it essentially short-circuit the cell’s normal controls, keeping aldosterone production switched on.21PubMed. Molecular genetics of Conn adenomas in the era of exome analysis
A small number of families carry inherited forms of the disease. The best characterized is familial hyperaldosteronism type 1, also known as glucocorticoid-remediable aldosteronism (GRA). It results from an unusual gene fusion between two neighboring genes on chromosome 8. The fusion creates a hybrid gene that places aldosterone production under the control of ACTH, the hormone that normally drives cortisol production, rather than the renin-angiotensin system. This means aldosterone fluctuates with the daily cortisol rhythm and can be suppressed by giving a small dose of a glucocorticoid like dexamethasone.22PubMed Central. Genetics of Primary Aldosteronism People with this form tend to develop hypertension early in life and have an elevated risk of hemorrhagic stroke.23PubMed. Frequency of familial hyperaldosteronism type 1 in a hypertensive pediatric population: clinical and biochemical presentation Other familial types (types II through IV) exist but are rarer and involve different genes. For the vast majority of patients, genetic testing is not part of routine workup unless the disease presents unusually early or runs in the family.
Primary Aldosteronism in Pregnancy
Pregnancy throws a wrench into the usual diagnostic approach. The renin-angiotensin-aldosterone system normally ramps up dramatically during pregnancy, which means the standard screening ratios and confirmatory tests become unreliable. Both confirmatory tests and adrenal vein sampling are generally contraindicated during pregnancy, so diagnosis often rests on finding suppressed renin alongside high aldosterone levels, a combination that is harder to interpret against the backdrop of normally elevated hormones.24PubMed Central. Primary aldosteronism in pregnancy
The clinical course varies widely. Some pregnant women with primary aldosteronism paradoxically improve because progesterone, which rises dramatically in pregnancy, can block the mineralocorticoid receptor and partially counteract aldosterone’s effects. Others develop severe, treatment-resistant hypertension with risks to both mother and baby. A systematic review found that complications occurred in about 62% of pregnant women with nonfamilial primary aldosteronism, but only about 19% of those with the familial type 1 form. Surgery during pregnancy did not improve outcomes compared with medical management alone.25PubMed. Management and Outcomes of Primary Aldosteronism in Pregnancy: A Systematic Review A case-control study found that women with primary aldosteronism needed more blood pressure medications after delivery and had slightly shorter pregnancies, though reassuringly, rates of serious adverse outcomes for mother and baby were similar to those in other high-risk pregnancies.26The Journal of Clinical Endocrinology & Metabolism. Assessment and Management of Primary Aldosteronism in Pregnancy: A Case–Control Study The standard MRA drugs, spironolactone and eplerenone, are generally avoided during pregnancy due to concerns about effects on fetal development, so management relies on other antihypertensives.
Aldosterone Synthase Inhibitors on the Horizon
The current medications for Conn syndrome work downstream of aldosterone: they block the receptor rather than stopping the hormone from being made. A new class of drugs called aldosterone synthase inhibitors takes the opposite approach. These agents target CYP11B2, the enzyme that performs the final step in aldosterone production, and are designed to be more than a hundred times more selective for that enzyme than for its close cousin CYP11B1, which makes cortisol. That selectivity is critical because knocking out cortisol production would cause an entirely different hormonal crisis.27PubMed. Aldosterone synthase inhibitors across the translational spectrum: Mechanistic foundations and emerging clinical applications
Several of these drugs are in clinical trials, including baxdrostat, lorundrostat, vicadrostat, and dexfadrostat phosphate. Early-phase results show significant reductions in aldosterone levels, blood pressure, and urinary albumin (a marker of kidney damage), with a lower risk of dangerously high potassium than traditional MRAs.28PubMed Central. The Emerging Role of Aldosterone Synthase Inhibitors in Overcoming Renin-Angiotensin-Aldosterone System Therapy Limitations: A Narrative Review However, long-term safety data and head-to-head comparisons with existing MRAs are still lacking.29PubMed. Aldosterone synthase inhibitors for the treatment of cardiovascular disease If these drugs prove their worth in larger trials, they could eventually change how bilateral primary aldosteronism is managed, offering a way to shut off excess aldosterone at its source rather than merely blocking its effects after the fact.
Mental Health and Quality of Life
An underappreciated aspect of Conn syndrome is its impact on mental health. Patients frequently report anxiety, depression, fatigue, and impaired quality of life that seem disproportionate to their blood pressure numbers. Some of this may be directly hormonal: aldosterone receptors exist in the brain, and chronic excess aldosterone can affect mood and cognition through pathways that are not fully understood. The Taiwan Society of Aldosteronism consensus has recommended mental health screening as part of the care of patients with primary aldosteronism, noting that early detection and management of psychological symptoms can improve overall outcomes.30PubMed. Targeted treatment of primary aldosteronism – The consensus of Taiwan Society of Aldosteronism Many patients report that their mood and energy improve significantly after surgery or appropriate medical treatment, even before blood pressure fully normalizes. If you have been diagnosed with primary aldosteronism and are experiencing persistent fatigue, low mood, or cognitive fog, it is worth raising these symptoms with your care team rather than assuming they are unrelated.