A 30 year old female presented with recurrent episodes of collapse with hypotension. She had been taking tramadol 100 mg four times daily for pain due to endometriosis. A random cortisol of 110 nmol/L led to suspicion of opiate induced adrenal insufficiency and further investigations were undertaken. Results 09:00 hours ACTH 3.2 ng/L, cortisol 109 nmol/L, fT4 12.3 pmol/L, fT3 3.7 pmol/L, TSH 1.18 mU/L, FSH 6.8 IU/L, LH 12.1 IU/L, prolactin 438 mU/L and IGF-1 14 nmol/L.
Short Synacthen test cortisol levels 0 min (09:00 h)182, 30 min 397 nmol/L.
Cortisol/ACTH profile (off opiates) following tramadol (half life 67 h) 100 mg orally confirmed a fall in both to trough sub-normal levels at eight hours.
Cortisol/ACTH profile (off opiates) following morphine sulphate (half life 1.54.5 h) 5 mg orally confirmed a fall in both to trough sub-normal levels at three hours.
On tramadol supine plasma renin activity (PRA) 0.6 nmol/L/h and aldosterone <100 pmol/L and post-ambulation PRA 1.4 nmol/L/h and aldosterone <100 pmol/L. Off tramadol supine PRA activity 1.0 nmol/L/h and aldosterone 170 pmol/L and post-ambulation PRA activity 1.6 nmol/L/h and aldosterone 253 pmol/L.
Glucagon test (off tramadol for 3 weeks) confirmed an impaired cortisol response of 304 nmol/L but a normal growth hormone response of 25.3 μg/L.
Whilst adrenal insufficiency due to opiates has been described previously this is the first report of an effect on the renin-angiotensin-aldosterone axis, possibly via suppression of renin secretion. The patient was advised that life-long hydrocortisone (and possibly fludrocortisone) supplements would be required to cover treatment with opiates.