Secondary adrenal failure and secondary amenorrhea due to hydromorphone treatment
Karsten Müssig1, Daniele Knaus-Dittmann1, Helmut Schmidt2, Klaus Mörike3 & Hans-Ulrich Häring1
Objective: Opioids are among the most commonly used symptomatic treatments of somatoform pain disorder. Human and animal studies suggest that chronic exposure to opioids suppresses the hypothalamo-pituitary-adrenal (HPA) and the hypothalamic-pituitary-gonadal axis. We report on a rare case of secondary adrenal failure and secondary amenorrhea due to hydromorphone treatment.
Case report: A 32-year-old female patient presented with fatigue, weakness, orthostatic dysregulation, dizziness, and secondary amenorrhea for three months. The patients past medical history revealed chronic pain syndrome (DSM-III-R) lasting two years. Four months before presentation, analgesic treatment had been changed to hydromorphone 32 mg BID and up to four times daily hydromorphone 2.6 mg as single dosages by a pain clinic. Decreased basal concentrations of plasma ACTH, serum cortisol, as well as mean 24-h urinary free cortisol excretion, and reduced peak responses of cortisol to ACTH 250 μg, to corticotrophin releasing hormone 100 μg, and during an insulin tolerance test with 0.5 IU insulin per kg body weight were consistent with secondary adrenal insufficiency. Estradiol levels were diminished with luteinizing hormone and follicle-stimulating hormone concentrations within the normal range, indicating secondary amenorrhea due to hypogonadotropic hypogonadism. Magnetic resonance imaging of the pituitary gland revealed no abnormal findings. The patient denied traumatic brain injury as well as skull radiation. After tapering from the benzodiazepine treatment we observed a stable increase to normal levels of the serum and urinary concentrations of cortisol as well as of ACTH, estradiol, FSH, and LH levels. The patient tolerated the treatment conversion very well. At the end of the tapering period she reported a clear improvement in vitality.
Conclusion: Clinicians should be alerted to the, though rare, endocrine side effects of hydromorphone treatment.