Clinical Case: A 56-year old woman with chronic pain syndrome on opioids presented from a nursing home with decreased level of consciousness and was found to be hypotensive requiring ICU admission. Several weeks prior to her presentation, she was hospitalized for progressive weakness and was found to have evidence of panhypopituitarism: low TSH (0.209 uIU/mL, nl 0.400 – 4.200), low free T4 (0.76 ng/dL, nl 0.80 – 1.50), low LH (<0.12 mIU/mL, nl 10.9 – 58.6), low FSH (1.7 mIU/mL, nl 16.7 – 113.6), and abnormal ACTH stim test (ACTH 6.4 pg/mL, nl 7.2 – 63; cortisol 0-min 3.8 mcg/dL, nl 6.7 – 22.6; 60-min 13.10). She was discharged on levothyroxine 25 mcg daily and prednisone 7.5 mg daily. On admission, her exam was notable for symmetric, non-pitting edema of the lower extremities to the knees with peau d’orange appearance. Initial tests revealed profound hypothyroidism with low TSH (0.381 uIU/mL), low free T4 (0.60 ng/dL), undetectable total T4 (<0.9 mcg/dL, nl 5 – 12.2), and undetectable free T3 (<1.00 pg/mL, nl 2.5 – 3.9). Thyroglobulin and TPO antibodies were within normal limits. Thyroxine binding globulin was low (6 mcg/mL, nl 13 -39). Additional biochemical studies re-demonstrated panhypopituitarism with low LH (<0.12 mIU/mL) and FSH (0.9 mIU/mL). Cortisol was elevated (73.2 mcg/dL) as she had received hydrocortisone. Despite fluid resuscitation and use of vasopressors, her hypotension persisted and she remained in critical condition. She was treated as a case of myxedema coma and started on full replacement dose thyroid hormone with 120 mcg IV levothyroxine daily and liothyronine 5 mcg every 8 hours. Over the next several days, the patient’s hemodynamics and mental status improved dramatically. A contrast-enhanced pituitary-protocoled MRI was notable for a moderately flattened sella (pituitary 3.5 mm in height) and absence of usual T1 bright signal in the posterior lobe. A work-up for causes of panhypopituitarism was mostly unremarkable: low IgG 4 (0.82, neg <1.50), indeterminate quant gold, negative HIV, low serum iron (35 mcg/dL, nl 50 – 200). Urine toxicology was positive only for opioids, reflective of the patient’s chronic pain regimen consisting of MS-Contin 60 mg twice daily and methadone 10 mg twice daily.
Conclusion: This case demonstrates the potential for chronic opioid use to suppress the hypothalamic-pituitary-thyroid axis and highlights the importance of maintaining an index of suspicion for hypothyroidism in this population.
Reference: (1) de Vries, F., Bruin, M., Lobatto, DJ., Dekkers, OM., Schoones, JW., van Furth, WR., Pereira, AM., Karavitaki, N., Biermasz, NR., Najafabadi, AHZ. Opioids and their endocrine effects: A systematic review and meta-analysis. JCEM. 2019. Doi: 10.1210/clinem/dgz022