Peptide Radiation Therapy Triggered a Dangerous Cortisol Surge in a Cushing Syndrome Patient | Research

The takeaway

A patient with ectopic Cushing syndrome from a thymic neuroendocrine tumor experienced a life-threatening cortisol crisis 5 days after starting PRRT, requiring emergency intervention.

Cortisol 141 µg/dL
Nearly 6x the upper normal limit, triggered 5 days after first PRRT dose in a Cushing syndrome patient

What the researchers found

PRRT triggered an acute ACTH-mediated hypercortisolemic crisis in a patient with ectopic Cushing syndrome, with cortisol reaching 141 µg/dL (normal: 5-25 µg/dL) and ACTH >2000 pg/mL, requiring emergency management.

Why it matters

PRRT is increasingly used for neuroendocrine tumors, but this case demonstrates that tumor lysis or stimulation during treatment can trigger dangerous hormone surges. Clinicians need to anticipate and prepare for this complication, especially in functioning tumors.

The numbers in context

Cortisol peaked at 141 mcg/dL (reference: 5-25). ACTH exceeded 2,000 pg/mL (reference: 10-60). Patient gained 8 kg in one week. Etomidate dose: 0.02 mg/kg/h IV. Crisis occurred 5 days after first PRRT cycle.

How the study worked

Case report documenting clinical presentation, biochemical findings, imaging, and management of PRRT-induced hypercortisolemic crisis.

Who was studied

One adult woman with metastatic ectopic Cushing syndrome from a thymic neuroendocrine tumor

What this study cannot tell us

Single case report — cannot establish incidence or risk factors; the mechanism (tumor lysis vs. radiation-induced hormone release) is speculative; management details may not be generalizable.

How to read the evidence

Single case report — lowest level of evidence but important for documenting rare adverse events and guiding safety protocols.

When this study was published

Published in 2025, timely given the expanding use of PRRT for neuroendocrine tumors.

The bigger picture

As PRRT use expands beyond the traditional GEP-NET setting, clinicians will encounter more patients with functioning tumors. This case is an important addition to the safety literature and may influence pre-treatment evaluation protocols for PRRT candidates.

Questions still open

Should patients with functioning neuroendocrine tumors receive prophylactic cortisol-blocking therapy before PRRT?
Is this complication predictable based on pre-treatment ACTH levels or tumor burden?
Should PRRT protocols include hormone monitoring protocols for the first week after treatment?

Common questions

What is peptide receptor radionuclide therapy (PRRT)?

PRRT uses radioactive atoms attached to small peptides that seek out and bind to receptors on neuroendocrine tumor cells. The radiation then destroys the tumor cells from the inside. It's an effective treatment but can sometimes cause tumors to release their contents, including hormones.

Why did the treatment cause a cortisol crisis?

The patient's tumor was producing excess ACTH, which drives cortisol production. When PRRT started destroying tumor cells, it may have triggered a massive release of stored ACTH, causing cortisol levels to spike dangerously — similar to a dam breaking.

Read the original research

Peptide Receptor Radionuclide Therapy-Induced Hypercortisolemic Crisis in Ectopic Cushing Syndrome.

JCEM case reports, 3(11), luaf226

View on PubMed ↗Publisher’s paper ↗

Citation

Pandit, Raghavendra; Yamichannaiah, Chethan; Lila, Anurag Ranjan; Karlekar, Manjiri; Memon, Saba Samad; Bandgar, Tushar. (2025). Peptide Receptor Radionuclide Therapy-Induced Hypercortisolemic Crisis in Ectopic Cushing Syndrome.. JCEM case reports, 3(11), luaf226. https://doi.org/10.1210/jcemcr/luaf226