By Manish Aghi, MD, PhD, Professor of Neurological Surgery and Co-Director of the Minimally Invasive Skull Base Surgery Center
Estimates from cancer registries suggest that pituitary adenomas are uncommon (with a prevalence of 19 to 28 cases per 100,000 people), particularly compared with solid tumors like breast, lung, and colon cancer.1 In contrast, a meta-analysis of autopsy data and radiologic studies performed in healthy volunteers indicates that pituitary adenomas are 700 times more common than registry data suggest and are found in 14% of autopsies and 23% of CT/MRI studies, giving a mean prevalence of 17%, or 1 in 6 people, with pituitary tumors and 1 in 600 with macroadenomas.2
Non-functional pituitary adenomas (NFPAs), pituitary adenomas that are not hormonally active, account for 15% to 30% of pituitary adenomas.1 The diagnosis of an NFPA is usually made either in the context of mass effect or, increasingly, during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated for NFPAs causing mass effect, but other aspects of NFPA management, including management of incidentalomas, preoperative endocrine work-up, postoperative follow-up, and management of remnant or recurrence remain controversial. To formulate guidelines addressing important questions about NFPA management, the Congress of Neurological Surgeons (CNS) Guidelines Task Force assembled a multidisciplinary taskforce of physician volunteers and evidence-based medicine trained methodologists to conduct a systematic review of the literature. It was an honor for me to lead this task force from October of 2013 until the guidelines were published in Neurosurgery in October of 2016.3
Topics we addressed included preoperative evaluation, primary treatment, treatment options for residual tumors after surgery, and postoperative patient management. For preoperative patient evaluation, the guidelines task force focused on preoperative imaging, preoperative laboratory evaluation, and preoperative ophthalmologic evaluation. For primary treatment, this guideline addresses surgical resection; medical therapy; radiation therapy; the natural history of untreated tumors; surgical methodologies such as endoscopy, microscopy, or craniotomy; and intraoperative adjuncts like neuro-navigation, CSF diversion, or intraoperative imaging. For residual tumor treatment, the guideline task force evaluated radiation versus observation. The task force also addressed postoperative patient management, including the frequency of postoperative imaging, postoperative endocrine evaluation, and postoperative ophthalmologic evaluation.
The guidelines task force organized the questions to be asked into seven broad topics: preoperative imaging; preoperative endocrine evaluation; preoperative ophthalmologic evaluation; primary treatment strategies; intraoperative techniques; management of residual tumor; and postoperative evaluation. A total of 300 articles met the inclusion and exclusion criteria for these seven topics. A complete reading of these 300 articles led the guidelines task force to produce a total of six level II recommendations and 24 level III recommendations for these seven topics.
While the lack of any class I evidence prevented our guidelines task force from putting forth any level I recommendations, some level II recommendations were able to be supported. First, for preoperative imaging, high-resolution MRI is recommended as the standard for pre-operative assessment of NFPA. For preoperative endocrine evaluation, routine evaluation of all anterior pituitary axes to assess for hypopituitarism is recommended because, beyond revealing a significant rate of deficits beyond the level of clinical suspicion for all pituitary axes, the cut-off values to initiate thyroid and adrenal replacement might be different in a patient with panhypopituitarism versus isolated deficiencies; routine prolactin testing is recommended in all patients with suspected NFPA to rule out hypersecretion that might not be clinically suspected; and replacement for adrenal insufficiency and significant hypothyroidism is recommended in all patients preoperatively. Surgical resection is recommended as the primary treatment of symptomatic patients with NFPA. When no residual tumor is present or only a small intrasellar tumor exists postoperatively, serial neuro-imaging studies are recommended. Radiosurgery and radiation therapy are recommended for treatment of residual or recurrent NFPAs to lower the risk of subsequent tumor progression. Specifically, radiosurgery using single session doses of 12 or more Gy or radiation therapy with fractionated doses of 45 Gy to 54 Gy are recommended for greater local tumor control rate of 90% or higher at 5 years following treatment.
Beyond these level II recommendations, several level III recommendations emerged from this process, which offer providers caring for NFPA patients a framework to help with decision-making. In the future, better powered studies will hopefully enable more high-level recommendations for NFPA patient management.
1. Davis FG, Kupelian V, Freels S, McCarthy B, Surawicz T. Prevalence estimates for primary brain tumors in the United States by behavior and major histology groups. Neuro Oncol. Jul 2001;3(3):152-158.
3. Aghi MK, Chen CC, Fleseriu M, Newman SA, Lucas JW, Kuo JS, Barkhoudarian G, Farrell J, Sheehan J, Ziu M, Dunn IF. Congress of Neurological Surgeons systematic review and evidence-based guidelines on the management of patients with nonfunctioning pituitary adenomas: executive summary. Neurosurgery. Oct 2016;79(4):521-523.