T2-weighted MRI intensity of GH-secreting adenomas varies depending on the tumoral heterogeneity, however T2-hypointensity predominates in most series of patients with acromegaly [28, 33]. The inconsistency in T2-weighted MRI intensity changes is more pronounced and differs from other types of pituitary adenomas, typically prolactinomas, which are constantly hyperintense on T2-weighted sequences [2, 12, 28]. The acromegaly literature concerning the assessment of preoperative T2-weighted MRI intensity changes to detect the amenability of complete resection and the rate of surgical remission via EETSS is still lacking. This study demonstrates a close relationship between the T2 signal intensity and the surgical remission rates, as an indicator of the degree of surgical resection completeness, in acromegaly. The surgical remission rates in the T2-hyperintense group are significantly lower than those of hypo- and isointense groups in newly diagnosed acromegaly patients. Based on these results, we belive that the T2 signal intensity changes in acromegaly may be a predictor of the degree of surgical resection and rate of remission following EETSS in pure somatotroph adenomas.
The interest in T2-weighted MRI signal intensity in acromegaly was first sparked by Hagiwara et al. [11]. Subsequently, T2W signal intensity was frequently examined as a method of predicting the effectiveness of somatostatin treatment in patients with acromegaly and incongruent data were reported [2, 15, 26]. The preferred reference tissue, in this regard, is decisive in order to standardize the results of T2W MRI intensity measurements across different centers and studies. Potorac et al., compared T2W signal intensity of adenomas with that of normal pituitary tissue, and this method was later postulated by Alhambra-Expósito et al., who similarly proposed the comparison of the signal intensity of pituitary adenomas to that of normal pituitary tissue whenever possible [2, 28]. In our study, quantitative assessment of T2-weighted signal intensity of GH-secreting adenomas is also employed and these results are compared to that of the temoral lobe cortical gray and subcortical white matter. In fact, the use of the gray matter as a comparator has been suggested because its similar signal intensity to that of the normal pituitary tissue [13]. Contrary to the already compressed and displaced normal pituitary gland due to the presence of the adenoma, the temporal lobe gray matter lacks any abnormality and preserves its natural configuration in cases with GH-secreting adenomas.
Several studies have frequently linked somatotroph adenomas to increased incidence of hypointensity on T2W MRI [2, 12, 28]. Accordingly, Potorac et al. and Alhambra-Expósito et al. reported a high prevalence of T2-hypointense GH-secreting adenomas, representing over 50% of their cases [2, 28]. This prevalence increased to 73% in the study of Tortora et al., when the T2-isointense group was neglected [33]. Interestingly, we found a predominance of T2-hyperintense group in our series (45%) and the T2-hypointense adenomas were detected in only 34% of our patients. Higher frequency of T2-hyperintensity and associated abundance of aggressive tumors in this series may be linked to the relative younger median age of acromegaly patients at diagnosis.
Hyperintensity on T2W MRI has been correlated with a significantly larger somatotrop adenoma size, more invasive and proliferative tumor behaviour and higher Knosp scores, indicating more frequent cavernous sinus invasion [4, 15, 23, 26]. Also, T2-hyperintense somatotroph adenomas were associated with less GH secretion and lower IGF-1 levels in previous studies [4, 15, 23, 26]. In line with these data, the GH and IGF-1 levels in our series are considerably higher in T2-hypointense group (Table 1). Although not statistically significant, the incidence of large and giant somatotroph adenomas in this study are higher in T2-hyperintense group than those of hypo- and isointense groups, nonetheless the frequency of suprasellar extension of the adenomas are found to be similar in all groups.
The molecular characteristics, although not completely understood, have been correlated with T2-weighted MRI signal intensity through the granulation pattern of the adenoma. Hypointensity on T2W MRI has been previously linked to a densely granulated cell pattern in acromegalic patients as described by Hagiwara et al. and the signal hypointensity has been attributed to the abundance of high protein content tissue due to the intense hypersecretory activity of densely granulated somatotropinomas [12, 29]. In this regard, less frequent optic chiasm compression and cavernous sinus invasion have been documented in densely-granulated T2-hypointense group among GH secreting macroadenomas [4]. Studies have also indicated close relationship between T2-hyperintensity on MRI and the sparsely-granulated adenomas in acromegaly [12, 26, 29]. Contrarily, sparsely-granulated somatotroph adenomas are generally considered as a rapidly growing tumor with an invasive nature and are larger at diagnosis, compared to densely-granulated tumors [1, 16]. However, the increased incidence of cavernous sinus invasion in sparsely-granulated somatotroph adenomas compared to densely-granulated tumors has been questioned and the results are inconsistent in the literature [13]. In our series, no statistically significant difference was found in between the T2-intensity groups for the size, the sellar floor and dural invasion and the Knosp grading of adenomas (Table 2). Our findings does not indicate a positive correlation between the granulation pattern of the somatotroph adenomas and the T2W MRI intensity characterisitcs.
The past decade has seen a number of acromegaly studies dealing with the changes in T2 signal intensity in order to predict the therapeutic response to medical treatment [14, 31]. In a a pioneer study evaluating the value of MRI as a predictor of therapeutic response in acromegaly, Puig-Domingo et al. demonstrated that T2 signal can identify responsiveness to somatostatin analogs in patients after unsuccessful surgery [29]. Similarly, Heck et al. reported that T2-hypointense adenomas had a better hormonal response to presurgically administered somatostatin analogs, suggesting that T2-hypointensity might be a useful pre-operative marker of somatostatin analogs response [13, 15]. An expanding body of evidence has led to the view that the presence of T2-hypointensity on sellar MRI predicts a favorable response to somatostatin analogs in GH-secreting pituitary adenomas [8, 10, 14, 19, 31, 33]. Accordingly, these findings raise intriguing question about whether T2-hypointense GH-secreting pituitary adenomas could be more amenable to complete resection as compared with T2-hyperintense and T2- isointense adenomas [28].
The literature has been inconsistent regarding correlation of GH tumor subtypes and surgical remission in acromegaly, as a result the surgical response based on GH tumor subtype is still to be determined [13, 17, 21]. In 2001, Mazal et al. reported a higher rate of incomplete resection and additional surgical interventions in patients with sparsely-granulated tumors [22]. Recently, Kiseljak-Vassiliades et al. emphasized that densely- granulated GH secreting pituitary adenomas had a much higher rate of remission in response to surgery compared to its sparsely granulated counterpart, 66% vs. 14% [19]. Contrarily, Brzana et al. did not find any significant difference between sparsely- and densely-granulated tumors [5, 13]. In this regard, the relationship between T2 signal intensity of the pituitary adenoma and the surgical remission rates in acromegaly patients undergoing EETSS has not been reported in the literature.
Our study presents the novel finding regarding the relationship between T2 intensity changes and the results of surgery for acromegaly and clearly demonstrates that the presence of T2-hyperintensity on preoperative sellar MRI predicts a unfavorable response to surgical treatment. In fact, the surgical remission rate for T2-hyperintense GH secreting pituitary adenomas in newly diagnosed acromegaly patients is significantly lower than that of the hypointense group. We believe that T2 signal intensity, apart from the granulation pattern of adenoma, has an independent predictive value for surgical remission acromegaly. In this vein, Potorac et al. suggest that T2-isointense GH secreting adenomas might in future be grouped along with hyperintense tumors into a single non-hypointense category that has significantly worse response rates to primary somatostatin analogs not only in terms of hormonal but also anti-tumoral effects [28].
In this study, total resection was performed in 72% of newly diagnosed acromegaly patients and no statistically significant difference was found between three T2 intensity groups in regard to the resection rates. Although all tumors in our study were macroadenomas, the incidence of large and giant adenomas were considerably higher in the T2-hyperintense group. Interestingly, no statistically significant difference was found for tumor size, a potential factor that may affect remission rates, in between the T2-intensity groups. Since the resection rates are not significantly different between the groups, we attribute the significantly lower remission rates in the T2-hyperintense group to the microscopic residues that could not be detected in the post-operative MRI.
In conclusion, preoperative T2-intensity may directly predict the probability of post-surgical remission as an important independent factor in patients with newly diagnosed acromegaly. Further support for this idea comes from recent guidelines for acromegaly management in which the potential utility of using T2 intensity to optimize patient management has been emphasized.