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Low Cortisol Caused by Quetiapine: Presented at APA

By Kristina R. Anderson

SAN DIEGO, CA -- May 23, 2007 -- Some patients taking the atypical antipsychotic quetiapine (Seroquel) are being diagnosed with ambiguously-presenting adrenal insufficiency, according to findings presented here at the American Psychiatric Association 2007 Annual Meeting (APA).

Specific management of adrenal insufficiency caused by antipsychotic use has not previously been studied.

"Adrenocortical insufficiency oftentimes presents ambiguously and with our case study, we had looked at many different causes for [the patient's] malaise before we ran an endocrine panel," said presenter Natalie Rasgon, MD, PhD, associate professor and director, behavioural neuroendocrinology program, Stanford University, and codirector, women's wellness program, department of psychiatry, Stanford University, Stanford, California, United States.

A 54-year-old male with a history of depression and posttraumatic stress disorder, who had previously been treated with psychotropic medications, quetiapine 300 mg/day and bupropion 225 mg/day, restarted his medications some 6 to 8 months after initial cessation. A previous recent admission to the hospital was for a urinary tract infection (UTI) and was treated with ciprofloxacin. He later presented to the hospital with fatigue, warmth, chills, loose stools, mild headache, and chest wall pain. Physical exam was relatively normal except for tenderness to palpation in the midclavicular line at the fifth rib. Laboratory results were also normal, except for elevated eosinophils levels that had previously been within normal limits.

The results of the man's work up for infectious, malignant, and rheumatological causes were all negative. "We decided at that point to look for endocrine causes as his symptoms became clearer," Dr. Rasgon said.

Early morning cortisol levels were low at 2.5 ug/mL. Cosyntropin stimulation test was performed with cortisol levels appropriately increasing from 4.2 mcg/mL to 20.4 mcg/mL, which made a primary adrenal insufficiency unlikely. Brain magnetic resonance imaging was negative for signs of a pituitary microadenoma, and testosterone, prolactin, and insulin-like growth factor concentrations were within normal limits; however, the adrenocorticotrophic hormone (ACTH) level was less than 5 pg/mL, suggesting secondary or tertiary adrenal insufficiency as the cause.

"At that point, we thought the 300-mg dosage of quetiapine had reduced the patient's ACTH and cortisol levels," Dr. Rasgon noted, so the patient was given a dose of prednisone 20 mg qam and another 10 mg qhs, "a significant dosage." The patient's condition improved quickly and markedly, at which point he was discharged and referred for follow-up to an endocrinologist and his psychiatrist.

Most symptoms of adrenal insufficiency are nonspecific, and misdiagnosis or failure to diagnose is a common occurrence, with about half of presenting patients having signs and symptoms of primary adrenal insufficiency for more than 1 year before a diagnosis is established.

Symptoms of adrenal insufficiency include weakness and fatigue, abdominal distress, anorexia, nausea and vomiting, myalgia or arthralgia, postural dizziness, salt craving, headaches, memory impairment, and depression.

Physical exam findings include increased pigmentation, postural hypotension, tachycardia, fever, decreased body hair, vitiligo, amenorrhoea, and intolerance to cold.

Quetiapine's 5-HT2 receptor blocking properties are thought to cause a strong inhibitory effect on ACTH and cortisol secretion. Other receptors blocked by quetiapine including dopaminergic, adrenergic, or histaminergic receptors might also be involved, according to the researchers.

"Although discontinuing the offending agent would seem appropriate, the risks of worsening the patient's psychiatric symptoms versus benefits of preventing adrenal insufficiency sequelae should be weighed," the study suggested.

Quetiapine is approved by the US Food and Drug Administration for the treatment of depressive episodes associated with bipolar I or II disorder.


[Presentation title: Adrenal Insufficiency Disguised and Quetiapine a Culprit. Abstract NR234]

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