Category: Adrenal Disorders
Objective : Cases of adrenal insufficiency (AI) secondary to Programmed Cell Death Protein 1 receptor ( PD-1 ) inhibitor have been increasingly recognized. We report a case of secondary AI due to nivolumab, a PD-1 inhibitor.
Methods : Case Report.
Results : A 48 year old postmenopausal female with metastatic melanoma, on nivolumab for 3 months, presented with fever, chills, abdominal pain, fatigue, and weight loss for one month. Physical examination showed a cachectic female with dry mucosa and perioral hypopigmentation. Body weight was 62 Kg ( BMI-22.1 kg/m2 ) and blood pressure was 87/58 mm hg. Initial laboratory findings showed sodium 128 (normal, 135-145 mmol/L ) and glucose 78 ( normal, 70-99 mg/dl ). Her morning serum cortisol was 0.1 (normal, 6.0-18.4 mcg/dl ). Cosyntropin stimulation showed an inappropriate response: cortisol increased from 0.2 to 3.6 mcg/dl after one hour. Adrenocorticotropic hormone was < 5 (normal, 0-46 pg/ml), which was consistent with secondary AI. Further workup showed that Thyroid Stimulating Hormone (4.08, normal 0.20-4.20microIU/ml), Free Thyroxine (1.2 , normal 0.9-1.8 ng/dl ) , Follicle Stimulating Hormone (FSH , 43.9 , normal 25.8-134.8IU/L) , Luteinizing hormone (LH , 62.9 , normal 7.7-58.5IU/L ) , Estradiol ( < 5, normal < 5 - 138 pg/ml ) , and Prolactin (12.9 , normal 3.4-24.1 ng/ml ) were within normal limits for a postmenopausal female. Insulin like Growth Factor-1 (IGF-1 , 55 , normal 57-95 ng/ml ) was borderline low. The patient was started on hydrocortisone, which improved her clinical status and lab findings. Nivolumab was discontinued. Five months later, a decline was seen in IGF-1, LH, FSH levels, but with sparing of the thyroid axis. MRI sella showed a normal pituitary gland, but was limited by lack of intravenous contrast. The patient had a complicated course with multiple hospital admissions and expired a year later.
Discussion : Nivolumab is a monoclonal antibody that binds to PD-1 receptor, allowing immune cells to mount a response against cancer cells. Nivolumab is currently used for treatment of metastatic melanoma. Endocrine abnormalities seen with nivolumab and other immunotherapy agents, include hyperthyroidism, hypothyroidism, AI (isolated primary or secondary), and hypophysitis. In our case, the patient developed secondary AI but later also developed decreased LH/FSH and IGF-1 function, but with normal thyroid function and pituitary imaging.
Conclusion : An increasing trend of endocrinopathies observed amongst oncology patients treated with immunotherapeutic agents necessitates a high clinical suspicion for diagnosis. We present a case of nivolumab induced secondary AI with later progression to hypopituitarism sparing the thyroid axis.
Kajal Shah– PGY2 Resident , Department of Internal Medicine, LIJ Forest Hills Hospital Northwell Health, NY ; Hofstra Northwell School of Medicine , NY., New York
Rifka Schulman– Assistant Professor, Hofstra Northwell School of Medicine; Director of Inpatient Diabetes ,Long Island Jewish Medical Centre, Division of Endocrinology, Long Island Jewish Medical Hospital, Hofrsta Northwell School of Medicine , NY.
PGY2 Resident , Department of Internal Medicine
LIJ Forest Hills Hospital Northwell Health, NY ; Hofstra Northwell School of Medicine , NY., New York
Kajal Shah, MBBS
Department of Internal Medicine, LIJ Forest Hills Northwell Helath , NY.
Assistant Professor, Hofstra Northwell School of Medicine; Director of Inpatient Diabetes ,Long Island Jewish Medical Centre
Division of Endocrinology, Long Island Jewish Medical Hospital, Hofrsta Northwell School of Medicine , NY.
Rifka Schulman MD , FACE , CNSC
Department of Medicine , Division of Endocrinology , Long Island Jewish Hospital , Hofstra Northwell School of Medicine , NY.