Endocrine Abstracts

Introduction: The spectrum of corticotroph cell pituitary adenomas is very wide, silent corticotroph adenomas (SCAs) being a rare subtype with positive immunohistochemistry for adrenocorticotropic hormone (ACTH), without causing Cushing’s disease. SCAs may exhibit a more aggressive behavior, and the changing of the clinical phenotype towards Cushing’s disease is described.

Case report: We present the case of a 74 years old, ex-smoker, hypertensive, male patient who was admitted to our clinic after sudden unilateral hearing loss, with no signs of hypercortisolism. Magnetic resonance imaging (MRI) of the pituitary showed a large mass of 14.3/15/12.3 mm. There was no opto-chiasmatic involvement and the hormonal profile revealed normal pituitary function with normal serum cortisol, suppressed after a 2 mg x 2 days dexamethasone suppression test (LDDST). The patient underwent transsphenoidal pituitary surgery. Postoperatively he did not have any pituitary deficiencies. Subsequently, 7 years after surgery, the patient is readmitted to our department, with central obesity, hypertension, dyslipidemia, and low bone mass. The hormonal profile showed an elevated ACTH (148.9 pg/ml), with elevated 8.00 a.m. serum cortisol, unsuppressed after a LDDST (14.74 µg/dl). Brain imaging showed a pituitary tumor of 17.9/18.8 mm with suprasellar extension, associated with bilateral adrenal hyperplasia on abdominal computed tomography (CT). Morphological and retroactive immunohistochemical (IHC) analysis of the pituitary tumor revealed strong positive staining for ACTH and weak immunostaining for TPIT; Ki-67 labelling index had a value of >3%. After neurosurgical evaluation found reintervention to be unfeasible, gamma knife radiosurgery was performed and therapy with dopaminergic agonists was initiated. The morning serum cortisol normalized, but remained unsuppressed after LDDST 2 years after radiosurgery, with ACTH values in regression under cabergoline 4 mg/week.

Conclusion: Bidirectional transformation of the clinical phenotype between Cushing’s disease and SCA is described, the time interval varying from 1 to 7 years. The silent phenotype is related to TPIT, the dysfunction of its expression being an early change in differentiation of this tumor type. SCAs are more biologically aggressive tumors than NFAs, therefore, close neuroimaging and clinical follow-up are mandatory. Also, patients with SCAs who present with postoperative residual disease should be considered for early adjuvant radiosurgery or long acting pasireotide.

References: Strickland et al (2021). Silent corticotroph pituitary adenomas: clinical characteristics, long-term outcomes, and management of disease recurrence, Journal of Neurosurgery, 135(6), 1706-1713.

Righi A et al. The changing faces of corticotroph cell adenomas: the role of prohormone convertase 1/3. Endocrine 2017; 56:286–97.