ACTH adenomas transforming their clinical expression: report of 5 cases

Abstract

OBJECT Adrenocorticotropic hormone (ACTH) adenomas have been recognized as a more aggressive and invasive subtype of pituitary adenomas. An additional and clinically relevant peculiarity of these tumors is their ability to modify their clinical expression from a silent form to Cushing disease or vice versa. The aim of this study was to review a series of patients with pituitary adenomas and analyze the clinical implications of the transformation of clinical expression in 5 cases that showed this phenomenon. METHODS The authors retrospectively reviewed a series of patients with pituitary adenoma and collected clinical, biohumoral, and neuroradiological data of those who presented with a transformation from silent ACTH adenomas to functioning tumors or vice versa. In all the cases, preoperative assessment consisted of brain MRI, ophthalmological examination, and complete baseline endocrinological investigation. In patients with clinical and/or biochemical findings suspicious for Cushing syndrome, a low-dose dexamethasone suppression test was performed to rule in or out this diagnosis. Endocrinological evaluations were repeated 1 month after surgery, 3 months after surgery, and every 6 months or annually thereafter. Ophthalmological evaluations and brain MRIs were repeated after 3 months and then every 6 or 12 months thereafter. RESULTS Five patients (2 men and 3 women) included in this series had corticotropic tumors that showed transformation from an endocrinologically silent form to manifest Cushing disease and vice versa. The mean age at presentation was 40 years (range 18–51 years). In 3 of these patients, a transformation from silent to functioning ACTH adenoma with manifest Cushing disease occurred. In 1 patient, the authors observed the transition from a functioning to a silent adenoma with spontaneous resolution of hypercortisolism. Another patient's silent adenoma “shifted” to a functioning adenoma and then regressed back to a silent form with spontaneous resolution of Cushing disease. This patient again developed hypercortisolism, which finally resolved spontaneously. In this series, the transformation occurred after a mean of 3.5 years (range 6 months to 7 years). The shift from an ACTH-silent to a functioning adenoma was observed in 9% of the ACTH-silent adenomas in this series (4 of 44 cases), and the spontaneous remission of Cushing disease to a silent corticotroph cell adenoma occurred in 1.5% of cases of this series (2 of 132 functioning ACTH adenomas). At follow-up (mean 107 months; range 60–177 months), cortisol levels were within normal limits in all 5 cases. However, 1 patient required Gamma Knife radiosurgery and eventually adrenalectomy for disease control to be achieved. CONCLUSIONS The ability of silent ACTH adenomas to transform their secretion pattern poses a challenge for neurosurgeons and endocrinologists. Because the transformation is often unexpected, the clinical and biochemical data can be underestimated. Furthermore, this bizarre and unpredictable postoperative tumor behavior can lead to misinterpretation of clinical and endocrinological outcomes. Even if these cases are very rare, they are not anecdotal in large series. Thus, ACTH adenomas require careful biohumoral and neuroradiological follow-up to detect possible transformations.