MON-111 - A Unique case of hormonal transformation in Metastatic Pituitary Neuroendocrine Tumor: Acromegaly to Ectopic ACTH Syndrome With Diabetic Ketoacidosis

Pituitary neuroendocrine tumors (PitNETs) rarely metastasize, and sequential secretion of multiple hormones is exceptionally uncommon. Functional transformation may create major diagnostic and therapeutic challenges.

Case Presentation:
A 34-year-old woman with prolactin-secreting pituitary adenoma diagnosed in adolescence underwent transsphenoidal resection in 2017 followed by adjuvant radiotherapy. She subsequently developed central hypothyroidism and adrenal insufficiency. In 2022, rising IGF-1 and growth hormone levels prompted evaluation revealing a paratracheal mass. Resection demonstrated metastatic neuroendocrine tissue. Additional metastatic lesions involving lung and axillary lymph nodes were resected in 2023; pathology from the axillary lesion stained positive for GH and prolactin with lymphovascular invasion and positive margins.
Progressive mediastinal recurrence in 2025 caused critical tracheal compression requiring tracheal stenting and temporary veno-venous ECMO support. During that hospitalization, new ACTH elevation with marked hypercortisolism raised concern for hormonal transformation to ACTH-secreting disease. She developed new diabetes mellitus and re-presented weeks later with diabetic ketoacidosis.

Results:
Despite HbA1c of 6.8%, she had profound insulin resistance requiring intravenous insulin infusion escalated to 66 units/hour with persistent glucose values >300 mg/dL before gradual improvement on high-dose basal-bolus insulin. DOTATATE PET/CT demonstrated avid disease in the pituitary region, mediastinal mass, axillary, and supraclavicular sites, supporting metastatic PitNET. Osilodrostat was initiated for hypercortisolism. Concurrent complications included upper-extremity DVT and bilateral pulmonary emboli. Repeat axillary biopsy was obtained for genomic sequencing, and she was transferred for peptide receptor radionuclide therapy (177Lu-DOTATATE).

Conclusion:
This case highlights an exceptionally rare metastatic PitNET with sequential prolactin/GH secretion followed by probable ACTH hypersecretion, resulting in acromegaly, Cushing syndrome, life-threatening airway compromise, and severe insulin-resistant DKA. Clinicians should consider hormonal evolution in progressive metastatic PitNET, particularly when abrupt metabolic deterioration occurs. Functional imaging and multidisciplinary therapy, including steroidogenesis inhibition and PRRT, may be critical in advanced disease.

*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.*