THU010 A Case Of Cushing's Disease Due To T-pit Positive, ACTH Negative Aggressive Corticotroph Pituitary Adenoma
Authors: Gopinath Chaitra , Pagadala Prathyusha , Choudhary Chitra , Tilden Daniel Robert 
Published: October 2023

Disclosure: C. Gopinath: None. P. Pagadala: None. C. Choudhary: None. D.R. Tilden: None.

Introduction: The 2017 WHO classification of Pituitary Adenomas utilizes pituitary transcription factors for its classification system. It can be helpful in identifying cell lineages in adenomas without expression of pituitary hormones. We describe a case of recurrent Cushing’s disease due to an ACTH negative, elevated Ki-67, TPIT positive aggressive corticotroph adenoma. Case report: A 54-year-old male presented with c/o diplopia, fatigue, decreased sexual drive. MRI brain showed a 2.4 x 1.4 x 1.6 cm sellar mass with suprasellar extension, displacement of the optic chiasm, extension into the left cavernous sinus. Hormonal work up showed evidence of central hypothyroidism (free T4- 04 ng/dl(0.6-1.6 NG/dl), TSH- 0.08 MCU/ml(0.35-5.00 MCU/ML) low testosterone (76 ng/dL(270-1070 NG/DL)),random cortisol of 20.1mcg/dL( 5.0-20.0 MCG/DL), ACTH- 136 pg/ml(7-63 pg/ml). Patient underwent transsphenoidal surgery (TSS). Pathology showed a pituitary adenoma of 1.5 cm with conspicuous mitoses and elevated Ki67 proliferation index (range- 15-35%). Immunohistochemistry was positive for prolactin; synaptophysin and negative for ACTH, GH, FSH, LH, TSH. Transcription factors for T-pit, Pit-1 and SF-1 were not assessed. Diagnosis of non-functioning adenoma was made. Repeat MRI showed residual tumor and due to elevated Ki-67, radiation therapy was recommended which was received at an outside hospital. 2.5 years later he was readmitted with profound hypokalemia, metabolic alkalosis and altered mental status. He appeared Cushingoid with facial plethora, moon facies, dorsocervical fat pad and violaceous striae on the abdomen. Dexamethasone suppression testing revealed elevated cortisol of 26.7 mcg/dl, AM cortisol -44.7mcg/dl (6.7-22.6mcg/dl),ACTH-280 pg/mL(7-63 pg/mL),24 hour urine free cortisol was elevated 2065 mcg/24 hour(3.5-45 mcg/24 hr). Given initial negative ACTH staining on the macroadenoma, there was concern for ectopic ACTH given acute presentation and absence of growth on the MRI compared to post radiation scans. IPSS was pursued which showed central ACTH source. Given stable size of residual tissue post radiation and location on MRI neurosurgery recommended against repeat surgery at this time. Patient was started on medical treatment for hypercortisolism with ketoconazole but had elevated liver enzymes limiting dose increase. Clinically patient continued to decline. Given significantly elevated cortisol with high risk of infectious and thrombotic events, poor short term outcomes decision was made for b/l adrenalectomy which he underwent successfully. Immunostains were ordered on the original adenoma resected and showed strong positivity for TPIT. Conclusion: Immunohistochemistry is an important step to aid classification of pituitary adenoma. Management of aggressive corticotroph adenoma with high ki-67 index can be a therapeutic challenge.

Presentation: Thursday, June 15, 2023