Clinically non-functioning pituitary adenomas (CNFPAs) are the second most frequent sellar tumor among studies on community-dwelling adults. They are characterized by the absence of hormonal hypersecretion syndrome, and patients present with compressive symptoms, such as a headache and visual field defects. Immunohistochemically, most CNFPAs are of gonadotrope differentiation, with only a few of them being truly null cell adenomas. Although these tumors express receptors for one or more hypothalamic releasing hormones, to what extent this has an impact on the biological and clinical behavior of these neoplasms remains to be defined. In this research, we evaluated the basal and hypothalamic secretagogue-stimulated intracellular calcium mobilization in 13 CNFPAs, trying to correlate this response to the phenotypic features of the patients. Our results indicate that the recurrence of a CNFPA correlates positively with cellular responsiveness, as measured by spontaneous intracellular calcium activity and the ability to respond to multiple hypothalamic secretagogues. We conclude that this finding may be a useful tool for predicting the clinicopathologic behavior of CNFPAs, by testing the variation of cellular responsiveness to hypothalamic secretagogues.

Phenotype transformation in pituitary neuroendocrine tumors is a little-known and unpredictable clinical phenomenon. Previous studies have not clearly defined and systematically concluded on the causes of this rare phenomenon. Additionally, the mechanisms of phenotype transformation are not well known. We reviewed cases reported in the literature with the aim of defining phenotype transformation in pituitary neuroendocrine tumors. We present an overview of the wide spectrum of phenotype transformation and its clinical features. We also discuss findings on the potential mechanism of this rare transformation, which may be related to PC1/3, the bioactivity of secretory hormones, gene mutations and the plasticity of pituitary neuroendocrine tumors. Clinicians should be aware of this rare phenomenon and more studies on the underlying mechanisms are required.

Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Nonfunctioning pituitary lesions represent a subset of pituitary adenomas that do not manifest with clinical features of hormone hypersecretion. Because of their indolent nature, their diagnosis is elusive, often resulting in presentation after the tumors have grown large enough to cause compressive symptoms. Although they are clinically silent, the various subtypes correspond to the predominant cell line of origin and therefore are biochemically distinct from one another. This article reviews the biochemical, clinical, and histopathologic features of each of these subtypes. A rubric is provided for diagnostic work-up of these lesions and the management options available to the treating clinician.

Silent pituitary adenomas are clinically non-functional (i.e., without clinically evident pituitary hormone production). The aim of this study was to investigate subjects with silent pituitary adenomas for possible variations in their clinical status. A total of 102 patients who had undergone surgery for pituitary adenoma and had been diagnosed with silent pituitary adenoma was included in the study. The patients' preoperative and postoperative hormonal parameters and magnetic resonance imaging (MRI) features were collected, and pathological specimens were re-evaluated. Immunohistochemistry results of the 102 patients were as follows: hormone-negative adenomas (n=35) 35.5%; FSH+LH-positivity (n=32) 31.3%; ACTH-positivity (n=11) 10.7%; α-subunit- positivity (n= 9) 8.8%; prolactin-positivity (n=8) 7.8%; GH-positivity (n=6) 5.4%; and plurihormonal adenoma (n=1). The mean sizes of SGA, SGHA, and SCA were 28.0±12.7, 30.0±16.0, and 27.7±8.9mm (p>0.05), respectively. With the exception of silent gonadotroph adenomas (SGAs), female gender dominance was shown in patients with silent growth hormone adenoma (SGHA) and silent corticotroph adenoma (SCA). Although no clinical relevance was observed in relation to hormonal excess, preoperative GH (4.21±4.6, vs. 0.27±0.36 p=0.00) was slightly more elevated in SGHA than in GH-negative adenomas. Additionally, preoperative basal ACTH values (47.3±28.7 vs. 23.9±14.4, p=0.003) were also higher in SCA compared to the other types. Our findings revealed SCAs to be of more aggressive behaviour than SGHAs and SGAs due to invasiveness in radiological imaging, their elevated re-operation, and postoperative ACTH values. Silent pituitary adenomas represent a challenging diagnostic tumour group. Careful initial evaluation of patients with pituitary adenomas should consider any mild signs and symptoms of functionality, particularly in cases of GH- and ACTH-secreting adenomas.