Endocrinology · Primary Bilateral Macronodular Adrenal Hyperplasia

Treatment Pathways: Surgery and Medical Support

At a Glance

For PBMAH-related Cushing syndrome, one-sided adrenal surgery may preserve adrenal function but can recur. Removing both glands controls cortisol permanently but requires lifelong steroids and emergency adrenal-crisis planning. Medicines can support surgery or help those who cannot have it.

Deciding how to treat Primary Bilateral Macronodular Adrenal Hyperplasia (PBMAH) is a highly personalized process. Because both adrenal glands are involved, the goal is to find a balance between reducing your body’s excess cortisol and maintaining enough adrenal function so that you don’t become entirely dependent on medication ^[1]^[2].

Your care team will look at the severity of your Cushing syndrome, your other health conditions (like diabetes or high blood pressure), and the specific size of your adrenal glands to recommend a path forward ^[3]^[4].

Surgical Options: One Side or Both?

Surgery is a primary treatment for many people with symptomatic PBMAH. There are two main approaches:

Unilateral Adrenalectomy (Removing One Gland)

This may be considered for selected patients with milder symptoms or Mild Autonomous Cortisol Secretion (MACS) based on a shared decision with your doctor ^[5]. The surgeon removes the “dominant” gland—the one that is larger or appears to be producing more cortisol on scans ^[6]^[7]. Specialized tests like Adrenal Venous Sampling (AVS) or nuclear scans are sometimes discussed at expert centers to help determine the dominant gland, though they are not routinely validated for PBMAH ^[8]^[9].

The Benefit: Many patients see significant improvement in their blood pressure (up to 82%) and blood sugar (up to 69%) while avoiding the need for lifelong steroid replacement ^[5]. Following unilateral surgery, temporary postoperative adrenal insufficiency can occur, requiring steroid replacement for a period of time ^[5].
The Risk: Because the remaining gland is also affected by the disease, the cortisol excess can return. In one retrospective series, while about 84% of patients went into remission initially, the long-term control rate was closer to 32% ^[10]. Over half of patients may eventually require a second surgery on the other side ^[5].

Bilateral Adrenalectomy (Removing Both Glands)

This is typically reserved for patients with severe, “overt” Cushing syndrome or those whose symptoms have returned after a one-sided surgery ^[1]^[10].

The Benefit: This is a definitive “cure” for the cortisol excess. Nearly all patients achieve immediate and permanent biochemical control ^[10].
The Risk: You will develop permanent adrenal insufficiency. This means your body can no longer produce its own cortisol or aldosterone (a salt-balancing hormone). You must take daily steroid replacements (usually hydrocortisone and fludrocortisone) for the rest of your life ^[11]^[12]. Failure to take these medications or manage them during illness can lead to a life-threatening adrenal crisis ^[13].

Medical Therapy: A Temporary Bridge

Medication is used as an essential tool in specific situations ^[14].

As a Bridge: If your cortisol is dangerously high, doctors may use medications to stabilize your body before surgery ^[15]^[16].
For High-Risk Patients: If you are not healthy enough for surgery or choose to decline it, medications can help manage the cortisol levels ^[17].

Common medications include:

Ketoconazole and Metyrapone: These “adrenostatic” drugs block the enzymes in the adrenal gland that produce cortisol ^[18]^[19].
Mifepristone: This drug does not lower cortisol levels; instead, it blocks the receptors so the cortisol cannot “attach” to your cells and cause damage. It can rapidly improve blood sugar and weight ^[17].
Osilodrostat: A newer, potent drug that can quickly suppress cortisol production in severe cases ^[20].

These medications require careful specialist management: Ketoconazole requires liver and interaction monitoring; metyrapone and osilodrostat can cause adrenal insufficiency, low potassium, or high blood pressure; and mifepristone has major pregnancy warnings and specific monitoring requirements since standard cortisol tests cannot be used to track its effect ^[18]^[20].

Choosing Your Surgeon

Because PBMAH is rare, it is vital to work with an endocrine surgeon who has deep experience with adrenal disease. You should not be afraid to “interview” your surgeon. Ask if they use a laparoscopic or robotic approach, which are less invasive and typically allow for a faster recovery, though the choice of surgical approach depends on lesion size, anatomy, and suspicion of malignancy ^[11].

Critical Surgical Considerations

If you choose bilateral surgery, you must have a clear “Sick Day Rule” plan in place before you leave the hospital, including an emergency kit with an injectable steroid ^[13].

Treatment Goal	Unilateral (One-Sided)	Bilateral (Both-Sided)
Primary Goal	Improve symptoms while preserving function	Permanent cure of cortisol excess
Recurrence Risk	High (>50% over time)	Almost zero
Daily Meds?	Temporary to none	Yes, lifelong (essential for life)
Adrenal Crisis Risk	Low	High (requires constant vigilance)

Common questions in this guide

When is one-sided adrenal surgery considered for PBMAH?

Removing one adrenal gland may be considered for selected people with milder cortisol excess or mild autonomous cortisol secretion. Surgeons usually target the larger or more active gland, but tests to identify a dominant gland are not routinely validated for PBMAH. This approach can preserve adrenal function, yet cortisol excess may return because the remaining gland is also affected.

What are the advantages and downsides of removing both adrenal glands?

Bilateral adrenalectomy removes the source of cortisol and provides immediate, lasting biochemical control for severe Cushing syndrome or recurrence after one-sided surgery. It also causes permanent adrenal insufficiency, so hydrocortisone and fludrocortisone are needed every day for life. Missing doses or failing to increase steroids during illness can cause a life-threatening adrenal crisis.

How often does Cushing syndrome come back after one adrenal gland is removed?

Recurrence is a significant concern because the remaining adrenal gland can also produce excess cortisol. In a retrospective series, about 84% of patients initially entered remission, but long-term control was about 32%, and more than half eventually needed surgery on the other side. Individual risk depends on disease severity and the treatment plan.

Which medicines can control cortisol in PBMAH?

Ketoconazole, metyrapone, and osilodrostat reduce cortisol production, while mifepristone blocks cortisol's effects without lowering the cortisol level. These medicines may be used before surgery or when surgery is not possible or is declined. They require specialist monitoring for liver problems, drug interactions, low potassium, high blood pressure, adrenal insufficiency, and pregnancy-related risks.

What lifelong care is needed after bilateral adrenalectomy?

After both adrenal glands are removed, you need lifelong hydrocortisone and fludrocortisone replacement because the body cannot make cortisol or aldosterone. Before leaving the hospital, ask for written sick-day instructions, an emergency injectable steroid kit, and a clear plan for illness, vomiting, or missed doses.

How should I choose a surgeon for PBMAH?

Look for an endocrine surgeon with deep experience in adrenal disease and ask how many adrenal operations, including PBMAH or BMAD cases, they perform each year. Ask whether laparoscopic or robotic surgery is appropriate for your anatomy and lesion size, and how they assess possible malignancy. The best approach depends on your individual anatomy, lesion size, and cancer risk.

Get notified when new evidence is published on Cushing syndrome due to bilateral macronodular adrenocortical disease.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

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This page explains treatment options for PBMAH for informational purposes only and does not constitute medical advice. An endocrinologist and experienced endocrine surgeon should tailor surgery, medicines, and steroid planning to your situation.