Relationship of Benzodiazepines with Serum Cortisol Levels: A Hidden Fact

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: SAT 0747-0780-Adrenal Case Reports 1 - CAH and Adrenal Insufficiency
Clinical
Saturday, June 21, 2014: 1:00 PM-3:00 PM
Hall F (McCormick Place West Building)

Poster Board SAT-0775
Sri Harsha Tella, MD1 and J Christopher Gallagher, MD2
1Creighton University, Omaha, NE, 2Creighton University Medical Cen, Omaha, NE
Background: Treatment with the benzodiazepines atypical antipsychotics is frequently associated with development of obesity, insulin resistance and drowsiness. Treatment-induced weight gain has been suggested to be the main contributing factor of diminished insulin sensitivity. Here we describe a case of benzodiazepine and antipsychotic medication induced hypocortisolism.

Case:We describe a case of 32 year old homeless Caucasian male with past medical history of anxiety, depression, bipolar disorder, obsessive compulsive disorder and opioid abuse (methadone) was brought into ER by squad as he overdosed himself with 15 pills of clonazepam 2 mg. Initial vital signs on presentation are Temp: 99.7 F, Pulse: 97/min, BP: 60-70/40-50 mm Hg, RR: 12/min. Chest X ray and CT head were unremarkable. He was transferred to the ICU for management of hypotension. He was given 8 liters of 0.9% normal saline over a period of 6 hours (including 3 liters of bolus) and blood pressure came up to 80-90/50-60 mm Hg. His laboratory evaluation showed normal electrolytes, creatinine and white count. Serum cortisol levels were tested which showed 1.7 mcg/dl at 04 50 AM and 0.6 mcg/dl at 06 00 AM. 250 mcg ACTH stimulation test was done which showed serum cortisol of 2.8 mcg/dl, 14.4 mcg/dl and 16.7 mcg/dl at 0, 30 and 60 minutes respectively. ACTH, testosterone, LH and TSH at baseline were 3.8 pg/ml, 979 ng/dl, 2.2 IU/l and 0.75 microIU/ml respectively. On further review of records, patient had normal blood pressures and serum cortisol in the past before the initiation of these medications. We discontinued clonazepam from his medication list and added prednisone 40 mg that has increased the blood pressures to normal range in our patient. He was discharged home on after fast taper with follow up in clinic which showed normal blood pressure in 1 month.

Discussion:Benzodiazepines and Opioids can cause endocraniopathy by acting on GABA receptors there by inhibiting the secretion of corticotrophin releasing hormone (CRH). In this patient, the acute drop in serum cortisol might be due to overdose of clonazepam that can inhibit CRH. This is interesting since CRF may have neurotropic effects related to the behavioral responses to stress, and the inhibitory effect thus may represent a mechanism of action for the anxiolytic effect of benzodiazepines. Surprisingly, this effect is dose dependent and can be seen as soon as 2 hours. So, in our patient this acute drop in blood pressures and cortisol levels are mostly likely related to more potent and efficacious benzodiazepine Clonazepam. 

Conclusion: Benzodiazepines can cause in acute lowering of serum cortisol levels and one should recognize this effect and treat accordingly to prevent the morbidity or mortality from acute drop in cortisol levels. Moreover, chronic use of opioids, antipsychotics and benzodiazepines can cause GABA induced suppression of CRH release leading to low cortisol levels.

1) Pharmacopsychiatry. 1986 Jan;19(1):19-22. —Benzodiazepine suppression of cortisol secretion: a measure of anxiolytic activity? —Gram LF, Christensen P.2) —Psychopharmacology (Berl). 1992;106(4):511-6. —Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers.

Nothing to Disclose: SHT, JCG

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