SAT-444 - An Unrecognized Endocrine Effect: Central Adrenal Insufficiency After Lu-DOTATATE Therapy

Introduction:
Lutetium-177-dotatate (Lutathera) is a peptide receptor radionuclide therapy that targets somatostatin receptor subtype 2 (SSTR2) that is used in the treatment of metastatic neuroendocrine tumors. It is generally well tolerated with its only known endocrinological side effect being neuroendocrine hormone crisis. Of note, SSTR2 is also present on the anterior pituitary gland, which regulates adrenocorticotropin hormone (ACTH) secretion. This raises the possibility of Lutathera targeting those receptors causing underrecognized endocrine adverse effects.

Case Description:
A 60-year-old female with stage IV pancreatic neuroendocrine tumor currently on Lutathera and lanreotide presented with dizziness and fatigue, with home blood pressures in the 90s/60s. She denied any history of chronic or concurrent steroid use. Laboratory evaluation revealed sodium 142 mmol/L (135-145), potassium 4.0 mmol/L (3.4-5.1), and a morning cortisol of 2.1 mcg/dL (5.2-22.5). Magnetic resonance imaging of the brain and abdomen noted no pituitary or adrenal abnormalities. Cosyntropin stimulation test revealed an inadequate cortisol response with a baseline cortisol of < 0.5 mcg/dL (3.4-22.5) and cortisol at 60-minutes was 7.1 mcg/dL (>=19.0) with a suppressed ACTH level of 2.3 pg/mL (7.2-63). She was initiated on hydrocortisone 15 mg in the morning and 5 mg in the evening with clinical improvement and outpatient endocrinology follow up.

Discussion:
This case highlights a rare and potentially first reported case of central adrenal insufficiency associated with Lutathera therapy. The mechanism is not fully understood but is thought to be from the off-target radiation effects on the somatostatin receptors present on the anterior pituitary gland leading to impaired ACTH secretion. Given that nonspecific symptoms, such as fatigue, nausea, and hypotension, are commonly seen in patients undergoing cancer treatment, diagnosis may be delayed. Early recognition and treatment is crucial in patients with adrenal insufficiency to reduce mortality. It is important to consider screening for adrenal insufficiency in patients receiving Lutathera therapy. Initiation of glucocorticoid replacement can help alleviate symptoms and prevent further life-threatening complications. Finally, more studies are needed to understand the mechanism and incidence of Lutathera-associated endocrinological dysfunction to better screen for endocrinopathies in this patient population.


References:
Sriram Gubbi, Mohammad Al-Jundi, Sungyoung Auh, Jaydira Del Rivero, Abhishek Jha, Marianne Knue, Joy Zou, Inna Shamis, Baris Turkbey, Jorge A Carrasquillo, Emily Lin, Karel Pacak, Joanna Klubo-Gwiezdzinska, Frank I Lin, Lutetium-177 DOTATATE Therapy Is Associated With Biochemical Endocrine Abnormalities in the Immediate Post-Treatment Period, Journal of the Endocrine Society, Volume 5, Issue Supplement_1, April-May 2021, Pages A1024–A1025,

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