How Do You Diagnose Conn's Syndrome of the Adrenal Gland?There are a number of tests that will help establish the diagnosis of Conn's Syndrome, but primarily we want to know if there is too much aldosterone being produced by one of adrenal glands since over production of aldosterone is the cause of this disease.
Lab Testing for the Diagnosis of Primary Hyperaldosteronism (Conn's Syndrome)The ARR Screening Test. The aldosterone to renin ratio (ARR) is the most reliable screening test for primary hyperaldosteronism. This is very easy to do and only requires one tube of blood to be drawn from your arm. Ask your doctor to get a simple blood test to check your plasma aldosterone concentration (PAC) and plasma renin activity (PRA). Classically patients with primary hyperaldosteronism have: Plasma aldosterone concentration (PAC) = HIGH, and Plasma renin activity (PRA) = LOW
If dividing the PAC by the PRA: PAC/PRA (this is called ARR; aldosterone-renin ratio). If the result is greater than 20, then the patient is very likely to have primary hyperaldosteronism. Classically, these patients will also have a low blood potassium level (hypokalemia), but in reality, less than half of patients have low potassium--most have low normal levels of potassium in the blood. a blood potassium level is a common blood test performed as part of a routine annual physical exam. Ask your doctor to go back and see if your potassium level has ever been low. Of course, if you must take extra potassium supplements then you are hypokalemic (you have low blood potassium). Remember only a third or so of patients with primary hyperaldosteronism have low blood potassium levels, but if you do there is a strong likelihood that you have primary hyperaldosteronism since there is really no other reason to have low potassium (except for some drugs like lasix).Blood pressure medications that can interfere with testing for Conn's Syndrome and hyper-aldosteronism.
- Spironolactone (Aldactone)
- Eplerenone (Inspra)
- Beta-blockers (Metoprolol, etc)
- ACE inhibitors
- Calcium antagonists
Thus, if you are getting your blood tested for aldosterone and renin, it is in your best interest to not be taking any of these drugs. Obviously, you can't stop taking any of these medications without talking specifically about it with your doctor. Almost all of these drugs will make the blood test for Conn's Syndrome error in the direction of saying that you do NOT have it when you do--they don't error in the direction of saying you DO have it when you really don't.
Should Blood Pressure Drugs be Stopped Prior to Testing for Aldosterone-Secreting Tumors (Conn's Syndrome)?Antihypertensive medications other than diuretics, should always be withdrawn for at least 4 weeks (6–8 weeks for spironolactone) before testing for an aldosterone secreting adrenal tumor causing Conn's Syndrome. Important! As discussed above, in many patients, this is not feasible because the blood pressure will go too high.
The most important medications to stay off during testing are Spironolactone (Aldactone), Eplerenone (Inspra), Amiloride. If your doctor says it is not safe for you to stop your blood pressure medications for a few weeks, it is still better to have your testing done while on medications than not be screened at all.
Testing in the morning. The ARR test is most sensitive and most accurate when samples are collected in the morning after patients have been out of bed for at least 2 hours, usually after they have been seated for 5–15 minutes. Given that the screening test can be affected by medications, it may have to be repeated once (a couple of weeks apart).
However, for most doctors diagnosing primary hyperaldosteronism is hard, time-consuming and sometimes confusing (the exception being only a few medical endocrinologists who are focused on endocrine hypertension and some kidney doctors; medical nephrologists with a focus on secondary hypertension). If you or your doctor want to run the laboratory tests by us, please do! We are here to help. Send us your laboratory results including what medications you were on during the testing.
In addition to evaluation the ARR screening test, it is important to review the absolute aldosterone value (a plasma aldosterone concentration; PAC >15 ng/dl is highly indicative of the disease). Also, the lowest detectable level of PRA should also be considered. Importantly, laboratories need to report individual values for both PAC and plasma renin activity (PRA)/ plasma renin concentration, as well as the ARR.
Classic Cases of Hyper-Aldosteronism and Conn's SyndromeAre you an "ALDO slam dunk"? Do you have classice hyperaldosteronism? So, to make things easier, let us start out with a text-book, classic patient with primary hyperaldosteronism. Are you an ALDO slam dunk? As you have read so far, arriving at the accurate diagnosis of primary hyperaldosteronism can be a bit tricky. However, this is easy for us. We evaluate patients with potential primary hyperaldosteronism EVERY DAY! Text-book cases are what we call ALDO slam dunks. These are patients it is so obvious that they have primary hyperaldosteronism, a third-year medical student should be able to pick it up. About 80 % of our patients with primary hyperaldosteronism are ALDO slam dunks. These are some of the characteristics of an ALDO slam dunk.
The Classic Patient with Hyper-Aldosteronism (Conn's Syndrome). The "ALDO Slam Dunk"
- High blood pressure (relative short duration)
- Tend to be female
- Young age (< 50 years old)
- Low blood potassium (hypokalemia)
- No other risk factors for high blood pressure (smoking, obesity, kidney disease, diabetes, etc)
- Very high plasma aldosterone concentration (PAC); >20 ng/dl
- Low (suppressed) plasma renin activity (PRA)
- Hypertension responding well to Spironolactone (or similar drugs)
- May have symptoms (frequent urination, muscle cramps, fatigue, etc.)
If you are an ALDO slam dunk, in a way, congratulations. (Note, we do not take it lightly that you have a disease, but this is fixable!). You do not need to undergo any more confirmatory testing. You can move 2 steps ahead straight to an adrenal-protocol CT scan (if you cannot tolerate intravenous contrast, you can have an adrenal-protocol MRI). You may not need to have the adrenal vein sampling, but rather move 2 additional steps ahead straight to what will likely be a curative adrenalectomy (Read about the PRA here).
All patients who are diagnosed accurately with unilateral primary hyperaldosteronism benefit from surgery, but women, and young patients tend to benefit the most. About 80 % of our patients with primary hyperaldosteronism are ALDO slam dunks. Yes, the operation will prevent you from developing future strokes, heart attacks, and arrhythmias (for instance, atrial fibrillation), and premature death.
Dr. Carling, Editorial note: Preventive medicine is popular in our culture nowadays, for good reasons. Of course, the idea to prevent future disease is great but sometimes it is easier said than done. There are some great examples, of course. Stop smoking and lose weight if you are obese is likely to prevent future disease. However, having an adrenalectomy for primary hyperaldosteronism may be one of the most effect preventive medical interventions to avoid future devastating diseases.
Dr. Carling, Editorial note: For our international patients, the measurements of plasma aldosterone concentration (PAC) and plasma renin activity (PRA) are typically expressed in conventional or SI (Systeme International) units, meaning pmol/l (not ng/dl), and pmol/l/min (not ng/ml/h), respectively. Do not worry about this. Dr. Carling is used to evaluating laboratory data from around the world and can easily make sense of this. It is helpful, though, to include the reference range of any assay from the laboratory when you send us your data.
Confirmatory Tests for Hyper-Aldosteronism and Conn's SyndromeSome patients are not an ALDO slam dunk and thus will need further testing. About 80 % of our patients with primary hyperaldosteronism are ALDO slam dunks, but that means about 20 % of patients need more detailed work up. This is where the confirmatory tests come in.
The first confirmatory test you should have done is to repeat the aldosterone to renin ratio (ARR) as it is the most reliable screening test for primary hyperaldosteronism. Again, screening is easy. Ask our doctor via a simple blood test to check your plasma aldosterone concentration (PAC) and plasma renin activity (PRA).
Borderline Cases... Not Quite Sure? The Endocrine Society (based out of the United States) guidelines recommend that patients with borderline (equivocal) ARR, and plasma aldosterone concentration (PAC) should undergo a confirmatory test to definitively confirm or exclude the diagnosis of primary hyperaldosteronism. One of the issues are that the medical endocrinology and medical nephrology experts have had difficulties in identifying what is the ideal confirmatory test. The Carling Adrenal Center recommends that you have a 24-hour urine collection of your aldosterone level. If this level is in the high upper normal range or frankly elevated, this proves that you have primary hyperaldosteronism.
However, the following (somewhat cumbersome) test have been advocated by some. These tests are very rarely needed these days and only the oldest doctors would venture into these bizarre and outdated tests:
- Oral sodium loading test
- Intravenous saline loading test
- Fludrocortisone suppression test
- Captopril challenge test
Its Time To Get A Scan! Once the confirmatory test proved that the diagnosis of primary hyperaldosteronism is accurate you may move ahead to the next step: adrenal imaging with an adrenal-protocol CT scan (if you cannot tolerate intravenous contrast, you can have an adrenal-protocol MRI). We have an entire section of this large website on scans and x-rays for adrenal tumors. Bottom line, there really is ONE first scan to get: a CT scan (CAT scan) with contrast. 90% of people with adrenal tumors need only ONE scan!
Molecular Genetics of Primary Hyperaldosteronism and Conn's Syndrome. Sporadic APAs are associated with somatic mutations of genes encoding ion channels: potassium channel KCNJ5, sodium-potassium ATPases ATP1A1 and ATP2B3, and the calcium channel CACNA1D. Interestingly, mutations in ion channel genes appear to be mutually exclusive with CTNNB1 mutations, which occur in about 5% of APAs. Germline mutations in KCNJ5, CACNA1D, and CACNA1H have also been identified and causes familial hyperaldosteronism. Another form of primary aldosteronism is caused by the fusion of a segment of the CYP11B1 gene with the CYP11B2 gene, causing aldosterone production to be inappropriately linked to ACTH stimulation. Familial hyperaldosteronism is usually associated with bilateral adrenal hyperplasia. Expand on this section
Clinical genetics - Special cases Germline mutations in KCNJ5, CACNA1D, and CACNA1H have also been identified and causes familial hyperaldosteronism. Familial hyperaldosteronism is usually associated with bilateral adrenal hyperplasia.