SAT-453 - A Rare Case of Combined Primary and Secondary Adrenal Insufficiency after Immune Checkpoint Inhibitor and Radiation for Metastatic Basal Cell Carcinoma

Introduction:
Immune checkpoint inhibitors (ICIs) are associated with multiple endocrinopathies, the most prevalent are thyroiditis and hypophysitis. Single gland involvement predominates, however multigland dysfunction happens in 1.4% of ICI patients. These patients are often exposed to other oncologic therapies, including radiation, which may independently contribute to endocrinopathies.

Case:
A 70-year-old male with a history of metastatic basal cell carcinoma diagnosed two years prior, presented with failure to thrive. He had been treated with the PD-1 inhibitor cemiplimab and abdominal radiation for metastatic disease with last treatment two months prior to admission. On presentation, the patient was hypotensive, hyponatremic, cachectic, with poor appetite. Morning serum cortisol was undetectable ( < 0.5 ug/dL), and repeat random cortisol also undetectable. Plasma adrenocoricotropic hormone (ACTH) was low ( < 1.5 pg/mL), raising concern for secondary adrenal insufficiency given ICI exposure. Pituitary MRI revealed a 4.0 mm hypoenhancement in the right anterior pituitary, likely representing a microadenoma. Other pituitary axes, including prolactin, IGF-1, and gonadotrophs were normal. TSH was mildly elevated at 5.8 uiu/ml with normal thyroxine levels consistent with subclinical hypothyroidism. Plasma renin and aldosterone levels were normal. ACTH stimulation demonstrated an inadequate response, with peak cortisol level of 3.6 u/dL at 60 minutes. Abdominal CT performed showed no signs of adrenal atrophy.

Given an oncologic treatment course that included both an ICI and abdominal radiation, radiation-induced primary adrenal insufficiency was considered as a potential etiology. However, the presence of a low serum ACTH level and lack of response to ACTH stimulation suggested concomitant secondary insufficiency as an additional or alternative contributor to hypocortisolism. The 4 mm microadenoma was felt to be an incidentaloma. Initiation of oral hydrocortisone led to rapid improvement in hypotension, appetite, energy, and mental clarity, with correction of hyponatremia.

Discussion:
This case highlights the importance of a comprehensive endocrine evaluation in patients treated with ICIs, particularly when presenting with features suggesting adrenal insufficiency, and the risk for endocrine dysfunction across multiple axes. While ICI-associated hypophysitis remains a recognized cause of secondary adrenal insufficiency, multiple immune mediated glandular disease or concurrent oncologic therapies such as abdominal radiation may also contribute. It is important for clinicians to maintain a high index of suspicion for multifactorial etiologies and consider the potential involvement of multiple endocrine glands when evaluating patients receiving ICIs. This is paramount for timely diagnosis and effective management of symptomatic patients.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*