Prevalence of endocrine dysfunctions with different opioids in chronic noncancer pain patients: a case-control study

BACKGROUND Opioid-induced endocrine dysfunction is often underappreciated, particularly in patients with chronic non-cancer pain (CNCP). OBJECTIVES To assess the prevalence of adrenal insufficiency and other endocrine disorders in patients with CNCP on long-term opioid therapy and compare opioid drugs and doses. DESIGN Case–control study. SETTING Pain Clinic outpatient consultations at a single tertiary centre. PATIENTS Adults of either sex with CNCP, either on opioid therapy for at least 6 months at morphine equivalent doses ≥25 mg day −1 (cases) or not receiving any opioid drug (controls), without recent (≤3 months) exposure to hormonal therapy or any opioid rotation in the past, were recruited between July 2020 and June 2023. MAIN OUTCOME MEASURES Prevalence of adrenal insufficiency, hypogonadism, hyperprolactinaemia, thyroid dysfunction, somatotroph dysfunction, and serum hormone levels. RESULTS A total of 201 patients were recruited, 32 controls and 169 cases with opioid therapy; 24 treated with morphine, 30 with fentanyl, 31 with oxycodone, 30 with tapentadol, 24 with buprenorphine and 30 with tramadol. The median overall morphine equivalent dose was 60.0 mg day −1 (mean treatment duration, 40.4 months). Adrenal insufficiency was found in 3.1% of cases and 3.3% of controls ( P > 0.999). Hypogonadism affected almost one-third (27.2% of cases and 31.3% of controls; P = 0.641) and was significantly more frequent with morphine than with other opioids. Hyperprolactinemia (8.9% of cases), thyroid dysfunction (1.2% of cases), and somatotroph dysfunction (7.7% of cases) did not affect controls and were significantly associated with opioid therapy in multivariable analyses. The following significant associations were also found: hypogonadism with a higher opioid dose; hyperprolactinemia and somatotroph dysfunction with the male sex; and elevated levels of some hormones with fentanyl. CONCLUSIONS Adrenal insufficiency was less common than expected and similar among cases and controls. Though uncommon, other endocrine disorders, with the exception of hypogonadism, were associated with opioid therapy. Moderate doses might explain the low prevalence, although males and patients on morphine or fentanyl may be particularly vulnerable.