First-Episode Psychosis and Cushing Syndrome

Posted on March 28, 2025 by MaryO

Cushing syndrome, a state of hypercortisolism, has multiple etiologies, including ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). EAS is a frequently severe emergency related to the degree of hypercortisolism. Neuropsychiatric symptoms of Cushing syndrome are well documented, including irritability, anxiety, depressed mood, and cognitive impairment.1 A few prior case reports have described first episode psychosis associated with Cushing syndrome,2 sometimes leading to delayed or misdiagnosis of Cushing syndrome.

Here, we report a case of a 72-year old man diagnosed with EAS caused by excessive ACTH secretion by a metastatic neuroendocrine tumor. Our report aims to add to the body of evidence indicating that Cushing associated psychosis can cause acutely severe paranoia and delusions that significantly impact management.

Case Report

Mr A, a 72-year-old retired physician with no prior psychiatric history, was diagnosed with new-onset psychosis in the setting of hypercortisolism. He initially presented with weakness secondary to hypokalemia and was found to have Cushing syndrome. On psychiatric evaluation, he demonstrated paranoia and delusions as well as illogical, concrete, and limited thought content. Laboratory workup, neurocognitive examination, and collateral history ruled out delirium or dementias. His morning cortisol levels were up to 162 μg/dL, and ACTH levels were greater than 2,000 pg/mL.

Mr A’s cortisol levels were not suppressed with a high-dose dexamethasone test, supporting ectopic ACTH production. He was found to have a metastatic ACTH secreting large cell neuroendocrine tumor, responsible for his hypercortisolism. Magnetic resonance imaging of his brain demonstrated a pituitary mass, and a bilateral adrenalectomy revealed a small focus of neuroendocrine carcinoma on his left adrenal gland.

Mr A was treated with haloperidol for hallucinations, delusional features, and paranoia; ramelteon for delirium prophylaxis; and suvorexant for sleep initiation. His endocrinology team ultimately started him on osilodrostat (decreases cortisol synthesis via 11 β-hydroxylase inhibition), which led to improvements in his cortisol levels, and his psychotic features subsequently diminished and resolved by the fourth day. All medications for psychiatric symptoms were successfully discontinued without symptom recurrence.

Discussion

Hypothalamic-pituitary-adrenal axis abnormalities, including hypercortisolism, have been well documented in first-episode psychosis cases.3 This includes increased morning cortisol levels in the blood in individuals with first-episode psychosis and increased baseline cortisol levels in the saliva for individuals at a clinical high risk of psychosis.4 There are multiple proposed mechanisms for how excess exposure to cortisol leads to psychosis. Theories include structural and chemical changes such as abnormal regulation of neurotransmitters, impaired neurogenesis, decreased brain volume in the hippocampus, abnormal loss of synapses, and dendritic atrophy. However, these changes are typically in the setting of prolonged exposure to high levels of cortisol.

There are a limited number of case reports regarding Cushing syndrome and acute psychosis.2 Past case reports that have described Cushing syndrome and acute onset of psychosis endorse severely high levels of cortisol, which may be a driving factor, and patients presented with less profound delusional and paranoid content.2 In this case, the patient presented with severe paranoia and delusions in the setting of excess cortisol and metastatic malignancy. Similar cases have been reported and focus on reducing cortisol levels to help manage the psychiatric symptoms.2,5,6 Psychotropic management can assist with symptoms; however, the ultimate treatment remains to address the endocrinologic abnormality. While most cases have reported improvement of neuropsychiatric symptoms with resolution of hypercortisolism, others have described persisting or even exacerbation of psychiatric symptoms even after resolution of the high cortisol levels.5–7 Most importantly, we must recognize Cushing syndrome and its hormonal derangements as a possible underlying etiology of psychosis to guide effective diagnostics and therapeutic management.

Article Information

Published Online: March 25, 2025. https://doi.org/10.4088/PCC.24cr03886
© 2025 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2025;27(2):24cr03886
Submitted: November 4, 2024; accepted January 3, 2025.
To Cite: Gunther M, Jiang S. First-episode psychosis and Cushing syndrome. Prim Care Companion CNS Disord 2025;27(2):24cr03886.
Author Affiliations: Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California (Gunther); Department of Psychiatry, University of Florida, Gainesville, Florida (Jiang).
Corresponding Author: Matthew Gunther, MD, MA, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Palo Alto, CA 94304 (guntherm@stanford.edu).
Relevant Financial Relationships: None.
Funding/Support: None.
Patient Consent: Consent was received from the patient to publish the case report, and information has been de-identified to protect anonymity.

References:

  1. Santos A, Resmini E, Pascual JC, et al. Psychiatric symptoms in patients with Cushing’s syndrome: prevalence, diagnosis and management. Drugs. 2017;77(8):829–842. CrossRef
  2. Okumura T, Takayama S, Nishio S, et al. ACTH producing thymic neuroendocrine tumor initially presenting as psychosis: a case report and literature review. Thorac Cancer. 2019;10(7):1648–1653. CrossRef
  3. Misiak B, Pruessner M, Samochowiec J, et al. A meta-analysis of blood and salivary cortisol levels in first-episode psychosis and high-risk individuals. Front Neuroendocrinol. 2021;62:100930. CrossRef
  4. Chaumette B, Kebir O, Mam-Lam-Fook C, et al. Salivary cortisol in early psychosis: new findings and meta-analysis. Psychoneuroendocrinology. 2016;63:262–270. CrossRef
  5. Al-Harbi SD, Mashi AH, AlJohani NJ. A case of Cushing’s disease presenting with isolated suicidal attempt. Clin Med Insights Case Rep. 2021;14:11795476211027668.
  6. Mokta J, Sharma R, Mokta K, et al. Cushing’s disease presenting as suicidal depression. J Assoc Physicians India. 2016;64(11):82–83.
  7. Pivonello R, Simeoli C, De Martino MC, et al. Neuropsychiatric disorders in Cushing’s syndrome. Front Neurosci. 2015;9:129.

From https://www.psychiatrist.com/pcc/first-episode-psychosis-cushing-syndrome/

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TO BE RESCHEDULED! Interview with Stephanie – PCOS, Possibly Cushing’s Patient

Posted on April 22, 2015 by MaryO

interview

The next interview on BlogTalk Radio will be rescheduled.  The Call-In number for questions or comments is (657) 383-0416.

Steph has a bio posted here: http://cushingsbios.com/2015/04/16/stephanie-steph-undiagnosed-bio/

The archived interview will be available after 7:00 PM Eastern through iTunes Podcasts (Cushie Chats) or BlogTalkRadio.  While you’re waiting, there are currently 82 other past interviews to listen to!

In her bio, Steph writes:

Hi. My name Steph, and this has been a long journey for me so far, and I see a long road ahead. Hopefully their will be a rainbow once all these clouds have melted away.

I just turned 33 years old (this month) and have been dealing with symptoms of Cushing’s since I was a pre-teen without even knowing it. I was diagnosed (or possibly mis-diagnosed) with PCOS when I was about 11. That’s when the irregular (to almost non-existent) menstrual cycles, hirutism (chin, upper lip, upper and lower thighs, fingers, toes, basically everywhere) and weight problems began. I was immediately put on birth control to regulate my periods, which only made my life a living nightmare. They forced on a fake (non-ovulating) period and made my moods a disaster. I went on to be on birth control until from the age of 11 until about 3 years ago when I just couldn’t take it anymore, and took myself off. I’ve been using herbal supplements for menstrual regulalation since then, and feel MUCH better.

Over the years I’ve always felt like there was something “more than PCOS” wrong with me. From the extreme inability to lose weight normally, and the ease to gain it, to the weak legs, vitamen d insuffeciency, high cholesterol, high blood pressure, extreme irritability, now non-existent cycle, shortness of breath (just from walking up 1 flight of stairs), slow healing, hoarse voice, high testosterone, male pattern baldness, blurry vision, EXTREME brain fog etc….. It has been very, very, very tough and emotional over the years. It has taken a toll on my personality, emotions, and those around me….

The way that I found out about cushing’s is rather unique. I was on a popular PCOS message board site called “soul cysters”, and I have always been EXTREMELY self conscience of my round puffy face, and was wondering if it could be a side effect of PCOS. So I searched Puffy face on the message board to see if others on the board had experienced it, and sure enough Cushing’s came up, and a suprising number of women either had both (cushing’s and PCOS) or had been mis-diagnosed, which apparently is very common with cushing’s. it was like a gigantic light bulb went off in my head when I started googling cushings symptoms. All these things that I have been experiencing almost my entire life started coming together. I’m really not crazy!! Everything is possibly related. Im almost 100% sure that this is it!!! I don’t know if this is a good or bad thing, as I see that cushing’s is curable in most cases, but it is also scary, and diagnosing it seems like hell!!

I have began my -already slow- journey to diagnosis. And, the the Dr.’s don’t seem to be all that well informed. However, I am DETERMINED. I am excited at the thought of possibly being able to get my life back through surgery or meds. I went to a well respected Endo in my area, and she is gonna test all of my hormones, including my cortisol level. Though she didn’t seem to be too informed on Cushing’s when I brought it up, along with my “dead ringer” symptoms. I’m going to a pulmonologist on the 29th as suggested by my GP (who also thinks I have cushings, but admits he’s not well informed enough or equipped to diagnose). I’m also going to an OBGYN soon (tried going to one today, and had to walk out because it was such a bad experience). But I am determined to get 2nd, 3rd, and however many opinions are needed until I am satisfied.

Also, on a side note, possibly having cushing’s, along with having PCOS, has made me look at the doctors and the medical profession as a whole in a different light. I feel like if you find a genuinely good doctor who listens, cares, takes you seriously, and is willing to test you without question, and work with you, your levels, and your symptoms, you are blessed!! I have had so many doctors try to push meds down my throat (for their own pockets/greed obviously) when it wasn’t needed or necessary without hesitation or question. And, then when I tell them that the medicine is affecting me adversely, they just tell me to keep taking it! It’s sad and ridiculous. I’ve had to learn to do my own research, know my own body well, and trust my own judgement…..

I will be praying for myself and everyone on this message board who has had to deal with this horrific symptoms over the years.

Updates coming…..

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Interview with Stephanie – PCOS, Possibly Cushing’s Patient

Posted on April 18, 2015 by MaryO

interview

The next interview on BlogTalk Radio will be Wednesday, April 22 at 6:00 PM eastern.  The Call-In number for questions or comments is (657) 383-0416.

Steph has a bio posted here: http://cushingsbios.com/2015/04/16/stephanie-steph-undiagnosed-bio/

The archived interview will be available after 7:00 PM Eastern through iTunes Podcasts (Cushie Chats) or BlogTalkRadio.  While you’re waiting, there are currently 82 other past interviews to listen to!

In her bio, Steph writes:

Hi. My name Steph, and this has been a long journey for me so far, and I see a long road ahead. Hopefully their will be a rainbow once all these clouds have melted away.

I just turned 33 years old (this month) and have been dealing with symptoms of Cushing’s since I was a pre-teen without even knowing it. I was diagnosed (or possibly mis-diagnosed) with PCOS when I was about 11. That’s when the irregular (to almost non-existent) menstrual cycles, hirutism (chin, upper lip, upper and lower thighs, fingers, toes, basically everywhere) and weight problems began. I was immediately put on birth control to regulate my periods, which only made my life a living nightmare. They forced on a fake (non-ovulating) period and made my moods a disaster. I went on to be on birth control until from the age of 11 until about 3 years ago when I just couldn’t take it anymore, and took myself off. I’ve been using herbal supplements for menstrual regulalation since then, and feel MUCH better.

Over the years I’ve always felt like there was something “more than PCOS” wrong with me. From the extreme inability to lose weight normally, and the ease to gain it, to the weak legs, vitamen d insuffeciency, high cholesterol, high blood pressure, extreme irritability, now non-existent cycle, shortness of breath (just from walking up 1 flight of stairs), slow healing, hoarse voice, high testosterone, male pattern baldness, blurry vision, EXTREME brain fog etc….. It has been very, very, very tough and emotional over the years. It has taken a toll on my personality, emotions, and those around me….

The way that I found out about cushing’s is rather unique. I was on a popular PCOS message board site called “soul cysters”, and I have always been EXTREMELY self conscience of my round puffy face, and was wondering if it could be a side effect of PCOS. So I searched Puffy face on the message board to see if others on the board had experienced it, and sure enough Cushing’s came up, and a suprising number of women either had both (cushing’s and PCOS) or had been mis-diagnosed, which apparently is very common with cushing’s. it was like a gigantic light bulb went off in my head when I started googling cushings symptoms. All these things that I have been experiencing almost my entire life started coming together. I’m really not crazy!! Everything is possibly related. Im almost 100% sure that this is it!!! I don’t know if this is a good or bad thing, as I see that cushing’s is curable in most cases, but it is also scary, and diagnosing it seems like hell!!

I have began my -already slow- journey to diagnosis. And, the the Dr.’s don’t seem to be all that well informed. However, I am DETERMINED. I am excited at the thought of possibly being able to get my life back through surgery or meds. I went to a well respected Endo in my area, and she is gonna test all of my hormones, including my cortisol level. Though she didn’t seem to be too informed on Cushing’s when I brought it up, along with my “dead ringer” symptoms. I’m going to a pulmonologist on the 29th as suggested by my GP (who also thinks I have cushings, but admits he’s not well informed enough or equipped to diagnose). I’m also going to an OBGYN soon (tried going to one today, and had to walk out because it was such a bad experience). But I am determined to get 2nd, 3rd, and however many opinions are needed until I am satisfied.

Also, on a side note, possibly having cushing’s, along with having PCOS, has made me look at the doctors and the medical profession as a whole in a different light. I feel like if you find a genuinely good doctor who listens, cares, takes you seriously, and is willing to test you without question, and work with you, your levels, and your symptoms, you are blessed!! I have had so many doctors try to push meds down my throat (for their own pockets/greed obviously) when it wasn’t needed or necessary without hesitation or question. And, then when I tell them that the medicine is affecting me adversely, they just tell me to keep taking it! It’s sad and ridiculous. I’ve had to learn to do my own research, know my own body well, and trust my own judgement…..

I will be praying for myself and everyone on this message board who has had to deal with this horrific symptoms over the years.

Updates coming…..

HOME | Sitemap | Adrenal Crisis! | Abbreviations | Glossary | Forums |Donate | Bios | Add Your Bio

Filed under: Cushing's, Interview, podcast | Tagged: , , , , , , , , , , , , , , , , , , , , , , , , , , , | Leave a comment »