PSAT039 Concomitant Primary and Secondary Adrenal Insufficiency in the Setting of Immunotherapy
Authors: Estrada Kathleen , Turcu Adina , Sandouk Zahrae , Esfandiari Nazanene H 
Published: November 2022

Abstract

Background
Secondary and, less frequently, primary adrenal insufficiency can occur following immunotherapy, but concomitant diagnoses have not been reported.

Clinical case
An 81-year-old woman with hypertension and history of well-differentiated papillary lung cancer, treated with left lower lobectomy and chemotherapy (Navelbine and Cisplatin) in 2008, and left upper lobe adenocarcinoma, treated with Cyberknife in 2019, presented with recurrent papillary like adenocarcinoma of the left lung and pleura in 2020. The patient was started on ipilimumab and nivolumab. A rash developed during the first cycle, and it was treated with topical steroids. After the second cycle, the patient developed weakness, worsening rash, and hyponatremia (Na 133 MEQ/L, n=135-144 MEQ/L). Additional laboratory tests showed: TSH 1.1 uIU/mL (n=0.45-5.33uIU/mL) with free T4 1.0 ng/dL (n=0.61-1.85ng/dL), ACTH 22pg/mL (n&lt;46pg/mL), and pm cortisol 6 µg/dL (n=8-23µg/dL). Secondary adrenal insufficiency was diagnosed related to immunotherapy, and prednisone 30mg daily was started. The patient 's weakness and hyponatremia resolved, and prednisone was tapered off. During the 3rd immunotherapy cycle, the patient developed recurrent rash and weakness. Labs showed hyponatremia (Na 125 MEQ/L), hyperkalemia (6.2MEQ/L, n=3.5-5.3MEQ/L), normal creatinine (0.96 mg/dL, n=0.44 - 1.03 MG/DL), late morning cortisol 12µg/dL, normal TSH (2.79 uIU/mL), and free T4 (0.93 ng/dL). Prednisone 40mg was started due to concern for adrenal insufficiency and immunotherapy was discontinued. Electrolytes did not improve, and the patient was hospitalized. Aldosterone was 7.3 ng/dL (upright &lt;= 39.2 ng/dL, supine &lt;= 23.2 ng/dL), direct renin was elevated (109.2 pg/mL, n=3.1 - 57.1 pg/mL). Fludrocortisone was added and the electrolytes normalized. A brain MRI showed a normal appearing pituitary gland, and abdomen/pelvis CT showed normal adrenal glands. Prednisone 20mg was continued and Fludrocortisone was tapered off. The patient subsequently developed recurrent hyponatremia and hyperkalemia with weakness requiring two more hospitalizations. During admissions, labs showed suppressed aldosterone (&lt;3 ng/dL, n= Standing: 4-31 ng/dL Recumbent: 1-16 ng/dL), elevated renin mass (91.8ng/dL, n=Upright: &gt;40 years 4-60 pg/mL &gt; 40 years 3-42 pg/mL), acute kidney injury (creatinine 1.69 mg/dL), suppressed ACTH (&lt;5 pg/mL), cortisol 29 ug/dL (while on prednisone), and positive 21-hydroxylase antibodies. Fludrocortisone was restarted and Prednisone 20 mg continued. Her electrolyte abnormalities, weakness, and renal insufficiency resolved.

Conclusion
Biochemical evidence of primary and secondary adrenal insufficiency was found in our patient. However, it is difficult to discern if the secondary adrenal insufficiency was due to immunotherapy or steroids until the steroids are tapered to physiologic levels and HPA axis is reassessed. Electrolyte abnormalities and positive 21-hydroxylase antibodies raise suspicion for primary adrenal insufficiency in this patient with low/suppressed ACTH and hypertension.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.