non- Functioning Pituitary Macroadenomas

 Non- functioning pituitary macroadenomas are by far the most common macroadenomas. They are also named non- secreting pituitary adenomas and, more recently, pituitary neuroendocrine tumours (PitNET). They are divided into eight subtypes, based on the immunohistochemical expression of anterior pituitary hormones and pituitary transcription factors .

They are revealed by symptoms of mass effect, such as headache and visual field defects, less frequently by anterior pituitary insufficiency. On the contrary, the presence of diabetes insipidus allows in nearly all cases to reject the diagnosis of pituitary adenoma. Non- functioning pituitary macroadenomas are also discovered by chance in more than 30% of the cases. The role of MRI is essential:

• to make the proper diagnosis and eliminate other sellar masses

 • to evaluate the optic chiasm and optic nerve compression

• to localize the normal pituitary gland

• to search for signs of aggressivity, such as cavernous sinus invasion

 • to look for remnants or recurrence after surgery.

Pituitary macroadenomas are centred by an enlarged sella turcica and frequently present with lobular contours. Tumoural extension is usually directed upwards to the suprasellar cistern, with compression and / or thinning of the optic chiasm and amputation of the inferior recesses of the third ventricle. Hyperintensity of the whole optic chiasm or a rail- like pattern on coronal T2- weighted images is a criterion of severity of nerve fibre lesion/ damage and must prompt rapid surgical decompression. It has been demonstrated that an angle less than 114 degrees measured between the optic nerve and the floor of the anterior fossa is a sign of poor prognosis despite surgery (Figure 1).

Fig1. Non- functioning pituitary macroadenoma on sagittal T1 (a) and coronal T2 (b) W images. A sagittal oblique contrast enhanced FIESTA (c) demonstrates the angle between optic nerve and anterior cranial fossa.

Giant non- functioning adenomas can extend to the frontal or temporal lobes. Blockade of the foramens of Monro can be responsible for hydrocephalus. Extension can also be directed inferiorly within the sphenoid sinus or laterally in the cavernous sinus, most of the times unilaterally.

on- functioning pituitary macroadenomas usually present with a moderate hypointense signal in T1 and a hyperintense signal on T2- W images. In large pituitary adenomas, T1 as well as T2 signal is usually heterogeneous, with areas of T1 hyperintensity and/ or T2 hyper- or hypointensity revealing haemorrhagic or necrotic phenomena. A fluid- fluid level indicates an old haemorrhage. In contrast, meningiomas most of the time display a homogeneous signal on T1 as well as on T2- W images. Post- gadolinium enhancement of the solid part of the tumour is variable but usually moderate. A characteristic microcystic pattern is observed on T2- W images in 50% of silent corticotropic adenomas. The normal residual anterior pituitary gland is visualized on T2 coronal images and after gadolinium infusion. It is compressed and pushed laterally on one side, against the cavernous sinus and superiorly, but almost never inferiorly. The opposite is true for meningiomas, craniopharyngiomas, and Rathke cleft cysts, where the normal gland is pushed down and can be seen inferiorly, below the tumour (Figure 2). The posterior pituitary bright spot is flattened and remains visible on axial T1 sequences; never theless, as soon as the tumour height reaches 20 mm, pituitary stalk compression leads to an ectopic vasopressin storage at the infundibular level.

Fig2. Coronal enhanced T1- W images demonstrating the normal anterior pituitary gland (arrows) in pituitary adenoma (a), sellar meningioma (b), craniopharyngioma (c), and Rathke cleft cyst (d).

Sequential coronal MRI exams obtained rigorously with the same projection, for instance in our practice perpendicularly to the subcallosal line, are mandatory to detect recurrence as early as possible (Figure 3).

Fig3. Sequential coronal T1- W images (a, b) are easily compared when obtained perpendicularly to the subcallosal line drawn on (c), sagittal T1- W image.

cavernous Sinus invasion Invasion

 of the cavernous sinus is usually obvious: enlargement of the laterosellar space, bulging of its lateral wall, blurring of the intracavernous veins with encasement but without narrowing of the intracavernous internal carotid artery make the diagnosis clear. Subtle invasion occurs initially at the posterior part of the cavernous sinus and is better identified on axial views. Integrity of the medial dural wall, more frequently visible on coronal or axial T2- W images at 3.0 T, excludes cavernous sinus invasion (Figure 4). In non- functioning pituitary adenomas, the cavernous sinus invasion, which represents a sign of aggressiveness, is usually unmodified by the surgeon/ usually persists after surgery and is a potential source of tumoural regrowth years after surgery.

Fig4. Non- functioning pituitary adenoma years after surgery with intrasellar and intracavernous tumoural remnant. T1- (a) and T2- W images (b). Flap of the medial wall of cavernous sinus (arrow).

Apoplexy

Apoplexy is a severe complication of pituitary adenomas resulting from an ischaemia or a brutal haemorrhagic event. Apoplexy is symptomatic, unlike subacute haemorrhage from which it has to be differentiated. Most pituitary apoplexies complicate pituitary middle- sized macroadenomas but rarely giant adenomas, as if haemorrhagic infarction preferentially occurs when the responsible pituitary adenoma is still contained by the sellar diaphragm. Not infrequently, apoplexy reveals the pituitary adenoma. Apoplexy of an adenoma remnant can also occur years after surgery. Diagnosis may be difficult in the early stage, the classical predominant hyperintensity on T1 being frequently absent; the T2 sequence is more sensitive by demonstrating heterogeneous low signal intensity. Diffusion- weighted images can show an increased signal intensity if compared with the normal brain and a low apparent diffusion coefficient. Thickening of the sphenoid sinus mucosa is present from the early stage (Figure 5). After gadolinium injection, peripheral enhancement is noticed with no or minimal enhancement of the central part of the sellar content.

Fig5. Pituitary apoplexy on coronal T1 (a) and T2 (b) W images. Thickened sphenoid sinus mucosa (arrows).

Sequential MRI will demonstrate the gradual increase in the T1 hyperintense signal, from the periphery towards the centre of the mass. If surgery is not indicated, as is usually the case, MRI will show shrinkage of the sellar content in several weeks or months.

the Postoperative Sella

In the immediate postoperative period, some neurosurgeons request for an MRI to eliminate a possible complication. But blood products and packing material can obscure the sellar content and possible residual tumour in the first weeks after surgery. Postoperative MRI is then usually not obtained before 3 months after surgery. At this time, blood and most of the packing material, if any, are resorbed at the exception of fat grafts which can persist many years after surgery. Coronal high- resolution 2 mm thick T2- W sequence is the most informative, whereas contrast enhanced MRI can frequently be spared. Remodelling of the normal pituitary gland occurs 6 months after surgery at the latest; it appears as a homogeneous triangular or oval small mass in contact with the sellar floor and the medial wall of the cavernous sinus, most of the times isointense to the brain cortex on T2- weighted sequences. The T2 signal of the tumoural remnant, if any, is quite always more or less hyperintense if compared with that of the residual normal pituitary tissue and of course the same as preoperatively. In subsequent years, MRIs rigorously performed with the same parameters and the same inclination will be able to demonstrate stability or an early slight increase in volume of the remnant and no change of the normal pituitary tissue (Figure6) .

Fig6. Pituitary adenoma remnant. Sequential T1- W images (a, b) show an enlargement of the remnant (asterisk). In c, coronal T2- W image, the normal pituitary gland (curved arrow) is unchanged and less intense than that of the tumoural remnant.

Prolactin- Secreting Pituitary Adenomas

In women with amenorrhea and galactorrhoea and a prolactin level above 35 ng/ ml, the chances to find a prolactinoma on MRI are very high. These adenomas display a T1 hypointense signal and a more or less hyperintense signal on T2 (Figure 7). When the clinical presentation is clear and the diagnosis confirmed by T1/ T2 MRI sequences, the protocol can be simplified and gadolinium injection avoided. Most are microprolactinomas and there is a good correlation between prolactin level and adenoma size. For instance, a prolactin level of 60– 90 ng/ ml usually corresponds to an adenoma of 7– 10 mm in diameter. Nevertheless, some adenomas do not obey this rule. A frank T2 hyperintensity reflecting degenerative changes or a T1 hyperintensity indicating a partial haemorrhagic transformation is less secreting and correlate with a lower prolactin level. Such a haemorrhage is usually asymptomatic and frequently seen at diagnosis as well as after cabergoline treatment. Prolactin levels above 150– 200 ng/ ml correspond to pituitary macroadenomas with suprasellar extension and/ or cavernous sinus invasion.

Fig7. Microprolactinoma hyperintense on T2 (a) and hypointense on T1- W images (b).

After cabergoline treatment, shrinkage of the adenoma occurs quickly, as soon as a few days or weeks and the hyperintense T2 signal increases. If pregnancy is obtained and cabergoline with drawn, the size of the adenoma roughly doubles when compared with its size before treatment. This has to be kept in mind for the management of prolactinomas during pregnancy. As a general rule, pregnancy has no adverse effect for microprolactinomas. Nevertheless, a close supervision has to be discussed in haemorrhagic adenomas, in prolactinomas with unusually T2 hypointense signal or T2 microcystic pattern or in women with a small sella.

In men, most prolactinomas are macroadenomas and even giant adenomas. In contrast with the usual T2 hyperintensity of prolactinomas, some harbour T2- hypointense areas corresponding to calcifications or amyloid deposits. Prolactin levels are very high, and can reach thousands of ng/ ml. Cavernous sinus invasion is very frequent. Extension to the entire sphenoid sinus can simulate an ear/ nose/ throat (ENT) cancer (Figure 8). Cabergoline is usually efficient with a rapid tumour shrinkage but can lead to a cere brospinal fluid (CSF) fistula in case of erosion of the sphenoid sinus walls. Initiation of treatment with low- dose dopamine agonists does not always allow to avoid this complication.

Fig8. Macroprolactinoma invading sphenoid sinus in a male. Prolactin level is 10 000 ng/ ml. (a) Sagittal T1- W image. Huge tumoural process extending upwards, downwards, and posteriorly. The inferior surface of the sphenoid bone is eroded as demonstrated on (b), sagittal CT (curved arrow). In (c), after low dose cabergoline, limited tumoural shrinkage leading to a CSF fistula. (d) Fat graft interposition to cure the fistula.

Growth Hormone- Secreting Pituitary Adenomas

 Growth hormone (GH)- secreting pituitary adenomas or somatotropinomas represent the third most frequent type of pituitary adenomas following prolactinomas and non- functioning tumours. Their prevalence ranges from 8 to 16% of all types of adenomas with an incidence of 3– 4 cases/ million inhabitants/ year.

Most of the times, somatotropinomas are revealed during the imaging studies that follow the diagnosis of acromegaly. Rarely, they can be an incidental finding on an imaging examination performed for a different reason in a patient that was not known to suffer from acromegaly.

Studies performed on large series of patients with acromegaly have shown that somatotropinomas are macroadenomas in over two- thirds of cases at diagnosis. The largest diameter of most GH- secreting adenomas is between 1 and 2 cm. Giant tumours are rare. There seems to be an inverse relationship between adenoma size and patient age at diagnosis, with younger patients often developing larger tumours. Among these younger patients, tumours develop more frequently in a genetic context and, when appearing before the closure of the growth plates, will lead to gigantism. The biochemical anomalies (GH and IGF1 increases) seem to also be related to tumour size with bigger tumours being responsible for higher levels of GH and IGF1. This is valid for adenomas measuring up to 20 mm of largest diameter. Beyond this threshold, correlations between secretory levels and tumour size are no longer found.

A particularity of the natural evolution of GH- secreting adenomas is their tendency to extend towards the sphenoid sinus. The reasons behind this propensity towards infrasellar development are not yet clear and may involve local effects of the somatotropinoma or the consequences of GH secretion on connective tissue. Suprasellar extension with optic chiasm compression is rarer than infrasellar extension, which explains why visual field defects are not very common at the diagnosis of acromegaly.

Unlike other types of pituitary adenomas, GH- secreting ones exhibit a T2- hypointense signal in around 50% of cases, whereas prolactinomas and non- functioning adenomas are more rarely T2- hypointense. Although different definitions of T2- weighted signal intensity have been employed in the existing literature, we believe that the most accurate one is comparison with normal pituitary tissue and, only when the latter is not visible, with the grey matter of the temporal lobe. T2- hypointense somatotropinomas present different characteristics compared to T2- hyper and isointense ones. T2- hypointense adenomas seem to be smaller, less invasive tumours, with higher secretory levels (Figure 9). These T2- hypointense GH- secreting adenomas respond better to somatostatin analogue treatment. This is true both for primary treatment in terms of de creases of GH and IGF1 and of tumour reduction and for adjunctive therapy following surgical failure with hormonal control being achieved more frequently in patients with T2- hypointense tumours.

Fig9. Growth hormone- secreting adenomas on T2- W images: T2 hypointense (a) and T2 hyperintense (b).

Current research is focusing on the relationships between T2- W signal intensity in somatotropinomas and histologic parameters. These might explain on one hand the different T2- W signal intensity of somatotropinomas and, on the other, the differences in adenoma behaviour, whether spontaneous or in response to somatostatin analogue treatment. Although not confirmed on large studies, it is believed that the densely granulated pattern of somatotropinomas correspond to T2- hypointensity, whereas T2- hyperintense adenomas are mostly sparsely granulated. Iron, fibrous tissue, or amyloid content do not seem to influence T2- W signal intensity. One study found that T2- hypointensity is correlated to expression of the somatostatin receptor type 5 (SSTR5), whereas no difference seems to exist with regards to SSTR2. Further detailed studies on larger series are required in order to clarify the matter.

corticotropic Pituitary Adenomas

Corticotropic pituitary adenomas are responsible for adrenocorticotropic hormone (ACTH)- dependent hypercorticism. Their detection is of major importance for the treatment of Cushing’s disease and represents a difficult challenge for radiologists. Less of half of corticotropic pituitary adenomas are macroadenomas. Most are microadenomas and a large number are picoadenomas (i.e. less than 3– 4 mm in diameter). Moreover, a significant number escape MRI detection even at 3.0 T. In these cases, inferior petrosal sinus blood sampling for plasma ACTH measurements has an important role. 11C methionine PET- computed tomography (CT) combined with 3D MRI is also very promising but for now is not able to detect the tiniest pituitary adenomas. Macrocorticotropic adenomas do not differ from other adenomas. They are hypointense on T1 and more or less hyperintense on T2- weighted sequences. Micro and picoadenomas can be located centrally or laterally in the sella, more readily posteriorly and in contact with the posterior lobe. They are suspected through the presence of a small or even millimetric T2 hyperintense area and confirmed by a localized enhancement defect on 3D MRI. Cavernous sinus invasion can be present even in microadenomas. Optimized MRI sequences are here mandatory, but increase the risk of false positive findings. Dynamic MRI has been proposed to distinguish ACTH- producing adenomas from non- functioning pituitary adenomas, the time- intensity curve of enhancement featuring a rapidly enhancing and slow washout pat tern in the first ones. However, dynamic imaging can lead to false positive images, particularly if a laterally positioned posterior lobe is not recognized (Figure 10). Delayed washout of corticotropic adenomas could also be demonstrated on a late postcontrast FLAIR sequence. Administration of corticotropin- releasing hormone (CRH) during 3T MRI has also been proposed to improve the detection of corticotropic adenomas. These data have to be confirmed in larger series of patients.

Fig10. False positive diagnosis of a pituitary microadenoma on early phase of dynamic imaging: the pseudo right defect in enhancement (curved arrow in a, coronal T1- W image) is related to a lateral normal position of the T1 hyperintense posterior lobe visible on (b) axial T1- W image.

Silent corticotroph pituitary adenomas are clinically and biologic ally silent, but harbour ACTH- secreting cells at pathology. Because they are endocrinologically silent, silent corticotroph adenomas are either diagnosed when large or incidentally and behave like non- functioning macroadenomas [10]. A cystic or microcystic pattern on T2- W images is present in more than 50% of silent corticotroph adenomas (Figure 11).

Fig11. Silent corticotropic adenoma. Microcystic pattern on coronal T2- W MRI.

اخر الاخبار

اخبار العتبة العباسية المقدسة

انعقاد الجلسة البحثية باللغة الإنكليزية ضمن فعاليات المؤتمر التمهيدي لألفية حوزة النجف الأشرف

مقالة علمية تناقش الأهمية البالغة في معرفة مشايخ الشيخ الطوسي (قدس سره)

دراسة علمية تثبت تاريخ تأليف الشيخ الطوسي لكتاب الفهرست

باحث يقدم دراسة علمية بعنوان (الشيخ الطوسي والكبرى الرجالية تأصيلًا وتطبيقًا)

المزيد

الآخبار الصحية

الشاي والقهوة وتدهور الذاكرة.. دراسة تكشف نتائج جديدة

هل يساعد الزنك على تحسين النوم والطاقة؟

علامات يجب عدم تجاهلها بعد تناول مكملات "فيتامين د"

لتجنب ارتفاع سكر الدم.. ما أفضل وقت لتناول الحلوى؟

المزيد

الآخبار التكنلوجية

الإمارات ترسخ مكانتها كأحد أبرز قادة الذكاء الاصطناعي عالميا !

"أوبن إيه آي" تحذر المشرعين الأميركيين من تحايل "ديب سيك" ؟

تصاعد التوتر بين "أبل" وإدارة ترامب.. ما السبب؟

سلاح طبي في ساحات الحرب.. رذاذ يوقف النزيف خلال ثانية !

المزيد

مواضيع ذات صلة

T pit Family of tumours

Pit- 1 Family of tumours

Pituitary Adenomas

Molecular Mechanisms of Carcinogenesis

Chronic Myeloid Leukemia, BCR-ABL Gene, and Disease Monitoring

Application of Liquid Biopsy to Non-small- Cell Lung Cancer Lung

Circulating Tumor DNA

Biomarkers in the Blood and in Tissues: A Complementary Approach

Biomarkers in Oncology: An Evolving Concept

Clinical Development of Venetoclax for Acute Myeloid Leukemia

Clinical Development of Oblimersen for Acute Myeloid Leukemia

Modalities for treating cancer