Case Presentation: A 34 year old male with a medical history of polysubstance abuse and hypothyroidism presented from subacute rehab after a combined thoracolumbar and sacral fixation surgery with worsening generalized weakness. The patient described deconditioning with increased difficulty standing despite 3-4 hours of daily physical therapy. Other acute symptoms included insomnia and mood swings. He was compliant with his daily maintenance methadone dose (50mg, started on discharge) and levothyroxine. Physical exam showed a deconditioned male with lower extremity alopecia. His strength was grossly 4/5 and his gait was unstable. Basic lab-work including CMP, CBC, and TSH were unrevealing. Serologic testing showed no evidence of a myopathy or immunologic disorder. MRI of the brain and spine excluded interval structural abnormalities or signs of a demyelinating process. Ultimately, the patient’s free testosterone levels resulted at 10 pg/mL (normal 35-155 pg/mL) and total testosterone 135 ng/dL (normal 250-1100 ng/dL). The patient was placed on clomid 50mg three times daily and subsequently showed improved strength over the following four weeks working with physical therapy.

Discussion: Managing opioid addiction is becoming increasingly common in hospital medicine as the national opioid crisis continues to evolve. Ensuring opioid addicted patients can maintain sobriety upon discharge is a primary focus of their inpatient care. Methadone is a synthetic full mu opioid receptor agonist with a slow absorption rate and long half-life that can deter patients from seeking a high from illicit opioid alternatives (1). Large clinical trials have shown that methadone is effective at keeping patients in drug treatment and at keeping patients from seeking exogenous opioid use (2). Side effects of methadone can include nausea, dizziness, arrhythmias, urine retention and sedation, however it is relatively safe to use when overseen by a knowledgeable provider (2). While heroine binds to mu receptors mostly in the pain and reward pathways of the brain, methadone also binds to mu receptors in the hypothalamus, where it blocks GnRH. GnRH is subsequently unable to stimulate the pituitary resulting in low FSH and LH levels (3). This disruption of the HPA axis results in hypogonadism and low testosterone in males, which can manifest as sexual dysfunction, muscle wasting, loss of body hair, insomnia, generalized fatigue and mood swings (3). Buprenorphine, a partial mu agonist, and alternative to methadone, exerts less of an effect on testosterone levels (4).

Conclusions: Hospitalists should remain cognizant of methadone’s testosterone-suppressing effects and treat individuals who develop a testosterone deficiency. Methadone induced hypogonadism should not be overlooked as it can cause distressing side effects and limit physical rehabilitation.