Psychosis Was 1st Sign of Cushing’s in Woman, 22: Case Report

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Hard-to-treat psychosis can be one of the first signs of Cushing’s disease, according to researchers in Saudi Arabia who detailed the case of a young woman with the disorder who was initially misdiagnosed.

The 22-year-old patient “presented to a psychiatry hospital before being referred to us because she resisted psychosis treatment,” the scientists wrote.

According to the team, this report highlights the need to conduct a thorough evaluation for possible rare causes of psychosis.

“Agitation with psychosis is likely the main obstacle for properly evaluating, diagnosing, and treating patients with Cushing syndrome,” they wrote.

The study, “Cushing’s Syndrome With Acute Psychosis: A Case Report,” was published in the journal Cureus.

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Up to 85% of patients with Cushing’s syndrome — a group of disorders that includes Cushing’s disease — experience psychiatric and mental problems, more commonly depression and irritability.

Other psychiatric manifestations, such as anxiety, mania, and psychosis, are rarer in Cushing’s, which is characterized by the presence of excessive levels of the stress hormone cortisol.

Here, the team described the recent case of a young woman who experienced psychosis as a first sign of Cushing’s.

The patient had developed an increase in appetite, was binge eating — consuming large amounts of food without being able to stop — and had gained weight over the previous three months. Within two weeks of symptom onset, she developed persecutory delusions and auditory hallucinations. These were accompanied by decreased need for sleep, agitation, irritability, and aggression.

The woman then went to a private psychiatry clinic and was instructed to take 10 mg of olanzapine, an antipsychotic medication, in the evenings.

However, after no improvements for a month, she was admitted to the psychiatry ward for evaluation. At this time, she developed cognitive symptoms, including impairments in memory, attention, and orientation.

No improvements were seen in the month following her admission while she was on the medication. Moreover, she developed fat accumulation in the face — referred to as “moon face,” a key symptom of Cushing’s — and high blood pressure.

Lab tests revealed she had lower-than-normal potassium levels in her bloodstream, called hypokalemia, as well as excessive levels of cortisol and adrenocorticotropic hormone (ACTH). ACTH drives the adrenal glands that sit on top of the kidneys to produce and release cortisol.

Other abnormal test results included elevated liver enzymes, and mildly elevated levels of certain fatty molecules called triglycerides.

An MRI scan of the brain revealed she had a lesion in the pituitary gland, consistent with a diagnosis of Cushing’s disease. She was transferred to the hospital and admitted to the endocrine department for additional tests. At admission, she had elevated blood pressure, heart rate, and respiratory rate, as well as elevated blood sugar (glucose) for which she was being medicated.

However, her clinical examination was made more difficult by her aggressiveness and lack of cooperation. Her medical and family history, however, revealed no signs of psychiatric illnesses or substance abuse. The patient also had not been on any medication prior to her admission.

After consultation with the psychiatry team, she was given olanzapine twice daily at a dose of 5 mg. This was combined with a 2 mg dose of lorazepam, given three times daily, to manage her anxiety. Lorazepam was delivered orally or directly into the vein (intravenously).

The patient was able to sleep and became calmer and more cooperative. She was being closely observed by a nurse, but this was discontinued after five days. Lorazepam also was reduced to two times daily.

She remained easily provoked, delusional and confused, with auditory hallucinations, however.

A second MRI scan confirmed a lesion in the pituitary gland and her blood cortisol levels dropped after a dexamethasone suppression test. This test is used to confirm the presence of hypercortisolism (elevated cortisol). It measures blood levels of cortisol in the morning after patients take a tablet of dexamethasone, a corticosteroid that normally blocks its production.

The diagnosis of Cushing’s disease also was confirmed by inferior petrosal sinus sampling, a procedure designed to measure ACTH levels in the veins that drain the pituitary gland.

The patient began treatment with 250 mg of metyrapone twice daily. Sold under the brand name Metopirone, metyrapone is a potent inhibitor of 11-beta-hydroxylase, an enzyme that plays a key role in cortisol production.

She then underwent microscopic transsphenoidal surgery to remove the pituitary lesion.

Post-surgery lab tests revealed normalization of ACTH and liver enzymes, although cortisol levels were below normal. Both blood pressure and sugar-controlling medications were tapered down and eventually discontinued.

Hydrocortisone tablets, commonly prescribed for lower cortisol levels, also were reduced and maintained for the two months following surgery. Cortisol levels then normalized.

Her symptoms of agitation and irritability, as well as delusion and auditory hallucination, eased. Importantly, her cognition and memory remained intact. As a result, medications were tapered down.

At discharge, due to side effects of olanzapine, she was switched to oral risperidone, administered at night. Oral clonazepam, a medication used to prevent and control seizures and treat panic disorder, was prescribed at a 0.5 mg dose, given twice daily as needed for agitation and psychosis.

During follow-up, the patient continued to experience psychosis and display abnormal behaviors. Both risperidone and clonazepam doses were increased and clonazepam was given more frequently (from two to three times daily, as needed).

Three months following her discharge, both agitation and irritability eased, and delusions and auditory hallucinations were no longer occurring.

Clonazepam was discontinued and risperidone was tapered down, with no re-emergence of symptoms.

Medications were scheduled for discontinuation at her next follow-visit. According to the researchers, the patient will continue to be monitored for signs of relapse.

“Cushing syndrome, like many other endocrine diseases, can present as treatment-resistant psychiatric symptoms, which may be missed and treated as a primary psychiatric illness due to the lack of proper assessment and management,” the authors wrote.

“Our case report gives an insight into possible rare secondary causes of psychosis and advice a thorough evaluation of patients,” they wrote.