Primary Aldosteronism, Sleep, and Why You Feel Like Crap in the Morning

If you have primary aldosteronism (also called Conn syndrome or PA), you already know this is far more than “just high blood pressure.” Excess aldosterone quietly damages the heart, blood vessels, kidneys, and brain. It also steals your energy. A lot of my patients say the same thing in clinic: I sleep, but I wake up feeling awful. Headache. Puffiness. High morning blood pressure. Nighttime bathroom trips. Fog. That is not in your head.

A new proof-of-concept study in Science Translational Medicine, by an international team led from the UK and Norway, offers a plausible explanation. They measured adrenal hormones in tissue, around the clock, including during sleep. The main finding is simple and important:

In primary aldosteronism, the worst aldosterone excess is not a flat, all-day elevation. It is a disrupted rhythm — and the disruption is worst at night and in the early morning.

That is exactly when you feel like crap.

1) Why a single morning blood test keeps missing this disease

Primary aldosteronism is common. It accounts for about 5 to 20% of hypertension and is still missed in the vast majority of patients. Guidelines now push toward screening everyone with high blood pressure, and that is the right direction. The problem is the toolkit.

Aldosterone is not a steady drip. It pulses. It has a daily rhythm. It is influenced by sleep, ACTH, potassium, salt, posture, and stress. One blood draw is a snapshot of a movie. Sometimes that snapshot looks “borderline” or even almost normal.

That is why so many patients are told they do not have PA — until the blood pressure will not come down, the potassium keeps falling, or they end up in an emergency room with a stroke or atrial fibrillation. Treating the blood pressure with more pills does not fix the toxic hormone source.

2) What this study actually did

The investigators used a wearable microdialysis system (U-RHYTHM) to sample free, unbound adrenal steroids from abdominal subcutaneous tissue every 20 minutes for 24 hours. Patients went home. They ate. They slept in their own beds.

They studied:

• 60 patients with confirmed PA (26 unilateral, 24 bilateral, 10 undetermined)
• 215 healthy comparison participants

Aldosterone was detectable in more than 96% of samples. So were cortisol, cortisone, and the hybrid steroid 18-hydroxycortisol. That last one matters. Hybrid steroids are chemical fingerprints of an adrenal gland that has gone off-script.

Figure 1. Aldosterone, cortisol, and other steroid hormone levels in PA patients versus controls, at different time points during the day. Red indicates very high levels, especially during late night and early morning.

3) The clock still works. The volume knob is broken at night.

Patients with PA still have a daily rhythm. Aldosterone, cortisol, and hybrid steroids still rise toward the end of sleep and fall after sleep onset.

Compared with healthy people, PA patients have substantially higher tissue aldosterone and 18-hydroxycortisol over 24 hours. The gap is not even across the day. It is largest from late evening through the early morning. Unilateral disease is worse. Nighttime and early-morning aldosterone and 18-hydroxycortisol are clearly higher in unilateral PA than in bilateral PA.

4) Pulses, hybrid steroids, and why unilateral disease looks different

Most individual PA curves are jagged: short pulses, then a dip that can land inside the healthy range, then another pulse. Unilateral patients throw the tallest nighttime peaks. Between pulses, the floor can look almost respectable.

The authors also looked at how tightly hormones move together on a 1-to-3-hour timescale. In unilateral PA, aldosterone and 18-hydroxycortisol were locked together about twice as often as in healthy people. After the overactive adrenal was removed, that coupling loosened and looked normal again.

5) What about cortisol?

Adrenal hypercortisolism (AHC), formerly called MACS or subclinical Cushing syndrome, is real in some PA patients, and it matters for the heart, metabolism, and recovery after surgery. In this particular cohort, it was not the headline.

Seven of 41 tested patients failed a dexamethasone suppression test. The precursor 11-deoxycortisol ran higher in PA, especially unilateral disease, particularly in the afternoon and night. Cortisone, cortisol’s inactive partner, ran lower overall and lowest in bilateral PA. In plain language: bilateral disease looked like relatively more cortisol exposure compared with cortisone during the evening and sleep. That lines up with the metabolic picture we already see more often in bilateral PA.

A failed dex test still deserves attention. This study simply says it is not the same thing as a smashed 24-hour tissue cortisol rhythm.

6) After the operation, the night goes quiet

Sixteen unilateral patients came back at three months after successful adrenalectomy. Every one of them had a 24-hour tissue aldosterone profile within the healthy range, or aldosterone so low it was unmeasurable in every sample.

That is the point of surgery: you become normal again. In this study, only surgery was shown to restore a normal 24-hour profile; pills were not tested in the same way. You are removing the source of the nocturnal pulses. Blood pressure can come down. Potassium can stay put. People stop feeling poisoned at dawn. (Not everyone normalizes completely: when the pathology shows multiple nodules or diffuse hyperplasia, some aldosterone excess can persist.)

At a high-volume center, this is usually a Mini Back Scope Adrenalectomy (MBSA) — a short, minimally invasive operation through small incisions in the back.

Bilateral disease is different. Those patients still have abnormal rhythms, just usually less extreme than unilateral disease. Many still benefit from expert evaluation, and some selected patients benefit from a more tailored surgical approach rather than being parked on medication forever. That decision has to be individualized.

Figure 2. After adrenal surgery, patients with PA normalize their diurnal aldosterone and cortisol levels. The night becomes still and quiet again!

7) What this means for you if mornings are the worst part of the day

It means your unrefreshing sleep is a clue, not a character flaw.

Nocturnal aldosterone excess is a plausible reason you:

• Wake with higher blood pressure than you went to bed with
• Feel puffy, tight, or headachy at dawn
• Cramp, or run a potassium that yo-yos
• Get up to urinate
• Look “not that high” on an afternoon aldosterone and get told everything is fine

If you have hypertension, low or low-normal potassium, suppressed renin, or an adrenal nodule, you need a proper PA work-up — not another year of adding blood pressure pills. Ask for an aldosterone and renin (the ARR). Do not let a single unimpressive number close the case if the clinical picture is screaming ALDO.

What Patients Need To Know

1. Primary aldosteronism is common, underdiagnosed, and more than high blood pressure.
2. Aldosterone is pulsatile. A single blood test can miss real disease.
3. The most abnormal secretion in this study was at night and in the early morning — which may be why so many patients feel wrecked on waking.
4. Unilateral PA had the highest nocturnal aldosterone and hybrid-steroid signals.
5. After curative adrenalectomy, those 24-hour aldosterone profiles normalized.
6. Cortisol rhythm was largely preserved here; PA does not automatically come with cortisol excess (AHC), though the two can coexist and both need expert evaluation.
7. Future diagnostics will move from static cutoffs toward rhythm-based analysis. We are not fully there yet.
8. Expert minimally invasive adrenalectomy can stop the nighttime hormone surge instead of just covering it up.

Moving Forward

If you have high blood pressure that never quite behaves, and mornings are when you feel the worst, do not accept “essential hypertension” as the final word. Get the right labs. Get the right imaging. If the disease is unilateral, get the right operation.

At the Carling Adrenal Center, we see this pattern every week: patients who were told their aldosterone was “not that high,” who still have a toxic nocturnal hormone rhythm, and who feel dramatically better when the source is removed. You deserve a precise diagnosis and an honest discussion of what surgery can realistically do for you — not a generic plan of more medication and another follow-up in six months.

If you or your doctor suspect primary aldosteronism, or you already have the diagnosis and want a second opinion, that evaluation is worth doing properly. Feeling like crap in the morning is not a personality trait. In many patients, it is a hormone rhythm that can be fixed.

Your blood pressure, your heart, your kidneys, and your quality of life are worth getting right.

Dr. Tobias Carling, of the Carling Adrenal Center, is one of the world's leading experts in adrenal gland surgery. Dr. Carling has performed thousands of adrenal operations over his career, including more than 2,400 since January 2022 alone. Dr. Carling left Yale University in 2020 to open the Carling Adrenal Center in Tampa, Florida.

To discuss the details of your case with Dr. Carling and become his patient, fill out the new patient form, and he will be in touch with you shortly.

Additional Resources: 

• Learn more about the Carling Adrenal Center
• Learn more about Dr. Tobias Carling
• Learn more about our sister surgeons at the Norman Parathyroid Center and Clayman Thyroid Center.
• Learn more about the Hospital for Endocrine Surgery
• Read about high blood pressure, parathyroid disease, and hyperparathyroidism here
• Changes in your blood pressure can also be related to thyroid disease. Read about thyroid disease, hyperthyroidism, and thyroid surgery here