Abstract Disclosure: A. Alzenaidi: None. Empty sella occurs when the pituitary gland appears shrunken or invisible and CSF fills the sella turcica space. It is commonly defined in the radiology literature as an incidental finding of no clinical significance, but an association with sequalae of lymphocytic hypophysitis (LH) was observed in a mouse model of the disease. However, patient data on the development of empty sella are scant and present later in life.To our knowledge, this is the second case of postpartum empty sella with clinically suspected LH and early presentation within 2 yr postpartum. A 31-year-old woman presented to our endocrine clinic for pituitary evaluation. She was 16 months post-spontaneous vaginal delivery with no history of excessive bleeding or blood transfusion. Her pregnancy was uneventful except for headache without visual changes after the thirty-fifth week, which improved with nasal steroid spray. Four to six weeks postpartum, she presented to her primary care physician with palpitations, fatigue and weight loss. Labs showed TSH, 0.001 mIU/mL (0.3-4.2); free T4, 30.98 pmol/L (9-19); free T3, 23.04 pmol/L (2.6-5.7); and thyroid peroxidase antibodies, 512.6 IU/mL (<5.6). Thyroid function tests improved after a short course of carbimazole, although without significant improvement of her symptoms. At 10 months postpartum, she presented to the ED with worsening fatigue, weight loss, vomiting and dizziness. Further history revealed oligomenorrhea and an inability to lactate since delivery. On exam, her heart rate was 100 b/m, respiratory rate was 20 b/m, BP was 90/50 mmHg, and temperature was 38.8 C. Labs showed WBC, 4.26 x 103/µL (4-11); Hb, 9.9 g/dL (11.8-14.8); PLT, 181 x 103/µL (150-450); Na, 136 mEq/L (135-145); K, 3.6 mEq/L (3.5-5.1); HCO3, 20 mmol/L (22-29); creatinine, 62 µmol/L (49-90); lactate, 0.82 mmol/L (0.5-2.2); FSH, 6.16 IU/L; prolactin, < 12.6 mIU/L (110-564) (prolactin prepregnancy was 233 mIU/L); TSH, 6.7 (0.3-4.2); free T4, <5.15 pmol/L (9-19); ACTH, 0.22 pmol/L (1.03-10.73); cortisol, 50.3 nmol/L (1.82 µg/dl); and peak cortisol after 250 mcg ACTH stimulation test, 223.5 nmol/L (8.1 µg/dl). She was treated with intravenous fluids and hydrocortisone. Pituitary MRI showed marked compression of the pituitary tissue with concave superior margins due to partially empty sella. She was maintained only on hydrocortisone replacement. During follow-up, her menstrual cycle resumed regularly, and fatigue and thyroid function improved (TSH, 2.65 µIU/ml; free T4, 12.13 pmol/L). Our patient had autoimmune thyroiditis with positive TPO antibodies, and it is possible that she had coexistent LH. LH typically presents as a pituitary mass; however, our patient had empty sella.In conclusion, the development of empty sella in this case suggests that postpartum atrophy of the pituitary gland can be life threatening if associated with hypopituitarism. Early recognition could prevent serious consequences. Presentation: Friday, June 16, 2023