Pituitary apoplexy: an update on clinical and imaging features

Most of the patients with symptoms related to PA will undergo computed tomography (CT) in an emergency setting. It is likely that, in most of them, the clinical suspicion might something other than PA. CT is effective in visualising pituitary expansive lesions leading to sellar enlargement (up to 94 % of cases) [5, 20, 25]. Because of the haemorrhagic component in most of PAs, CT will show patchy or confluent areas of hyperdensity within a pituitary lesion (Fig. 1) [5, 14, 20, 25]. Although a hyperdense lesion inside the sella turcica tends to represent PA in the proper clinical setting, diseases other than PA may lead to similar radiological pictures. The most common hyperdense lesions in the pituitary region are aneurysms, meningiomas, Rathke cleft cysts, germinomas and lymphoma. They can be easily differentiated from blood using MRI. After administration of contrast medium, a rim of enhancement may be the sign of pituitary apoplexy [40]. The real accuracy of CT in the diagnosis of PA is not fully described, being dependent on the time of imaging from onset of symptoms and on technical characteristics of CT itself. Some authors demonstrated a low sensitivity of CT in detecting pituitary tumour haemorrhage; this ranges from 21 % [20] to 46 % [16]. A possible explanation for these wide ranges is related to blood degradation, leading to a decreased density, in the days following the acute onset. For this reason, making the distinction between cystic or degenerative changes inside a pituitary neoplasm and a subacute haemorrhage may be impossible [14]. Based of the above-mentioned data, it is important to remember that the CT examination may be normal, underestimated or non-pathognomonic, especially in those rare patients with non-haemorrhagic PA or without a pre-existing pituitary adenoma. Therefore, although CT can exclude other diseases (i.e. subarachnoid haemorrhage), an MR examination can give more details about a suspected PA [14, 20].

Magnetic resonance imaging (MRI) is the most important tool in the diagnosis of PA, being able to identify the presence of an adenoma and its haemorrhagic degeneration. MRI is definitely superior to CT in the diagnosis of PA with a sensitivity ranging from 88 % to 90 % [18, 41]. Recently, Semple et al. demonstrated that MRI features of PA correlate with the pathologic reports and operative findings and that PA features can be accurately predicted from MR imaging [14].

It is well known that the signal of blood clots in MRI changes over time. In the acute phase (0–7 days), deoxyhaemoglobin leads to shortening of the T2 relaxation time due to the susceptibility effect and the MRI signal is hypointense on T2-weighted imaging (T2W1) with isointensity or slight hypointensity on T1-weighted imaging (T1WI) (Fig. 2). In the subacute phase (7–21 days), methaemoglobin shortens the T1 relaxation time and the haemorrhage will appear hyperintense on T1WI as well as on T2WI (Figs. 3 and 4). In the chronic phase (>21 days), macrophages digest the clot and the presence of haemosiderin and ferritine causes a strong hypointensity on both T1WI and T2WI [42‐44].

First, Poitin et al. and, more recently, Dubuisson et al. described the MRI features in a group of patients with PA [5, 45]. MRI predominantly showed an intra- and suprasellar expanding mass with different signal intensities on T1WI and T2WI, depending on the presence of haemorrhage and on its stage, as described above. In most cases, MRI performed during the acute phase of the clinical syndrome shows areas of hyperintensity on T1W1, generally more pronounced in the peripheral area of the lesions [45]. After IV gadolinium administration, a slight and inhomogeneous contrast enhancement is evident (Figs. 3c, f, 4) but often is difficult to differentiate from normal residual pituitary gland [5, 14, 45, 46]. T2WI showed areas of mixed high and low signal intensity, with the presence of a possible thin peripheral ring of marked hypointensity, representing haemosiderin and ferritin deposition. The latter must be considered an unusual and unexpected finding, since pituitary tumours lack a blood-brain barrier, and the accumulation of macrophages containing haemosiderin normally does not occur [45]. T2WIs are even useful in the evaluation of potential compressions of the optic chiasm and hypothalamus by the tumour [40].

Many authors [5, 14, 45] described the possibility of a fluid debris level within the mass. Poitin et al. made a pathological-radiological correlation in their patients with this finding, showing that the upper fluid (hyperintense on T1W1) contains free extracellular meta-Hb and the lower layer (iso-hypointense on T1WI) corresponds to a sediment of red blood remnants [45]. This finding is suggestive of late subacute haemorrhage and is considered a specific sign of pituitary apoplexy [45‐47].

Another important MRI finding that is highly indicative of PA is the thickening of sphenoid sinus mucosa (Fig. 3a) [14, 46, 48]. This condition may be related to venous engorgement in this region, a reversible condition on follow-up studies [14]. Thus, this is considered a specific finding of the acute phase of haemorrhage.

Less is known about the MRI appearance of pituitary apoplexy without haemorrhagic infarction. Ostrov et al. found that this condition may appear as low signal intensity on both T1WI and T2WI, without contrast enhancement inside the lesion but with a peripheral rim of enhancement [49]. It has been reported that diffusion-weighted images may help to visualise areas of infarction within a non-haemorrhagic pituitary lesion [15] but obtaining good DWI images in the pituitary region is challenging because of susceptibility artefacts.

The use of T2*-weighted gradient-echo (GE) MR imaging is currently the most sensitive neuroimaging technique for the identification of brain haemorrhage. T2*-weighted images are highly sensitive to the paramagnetic effects of deoxy-HB and meta-HB and show bleeding products and haemosiderin deposits as areas of strongly hypointense signal. Tosaka et al. recently demonstrated that this statement could be applied even to PA [50]. GE MR can depict acute and chronic haemorrhages not seen with conventional SE techniques. These can appear as a hypointense rim, mass, spot or diffused area of lower signal intensity. The latter, diffused, is related to pituitary adenomas without a history of headache or clinical PA.

MRI is a useful tool in the differential diagnosis of pituitary apoplexy. Many conditions can present with hyperintensity  on T1WI in the sellar region, the most frequent MRI feature of PA [46]. Thus, it is important to use advanced MRI techniques such as T2*GE together with a careful search for specific radiological findings, such as fluid levels or thickening of the sphenoid mucosa.

The posterior lobe of the pituitary gland usually appears as a hyperintense spot on T1WI because of storage of vasopressin [51‐53]; this is a normal finding and should not be confused with a haemorrhage within the gland.

In the case of anterior pituitary lobe hyperactivity, the gland may be hyperintense [54, 55]. In these cases, haemorrhage can be easily excluded with the evaluation of T2WI and T2*WI.

Another condition to consider for the differential diagnosis is the presence of an aneurysm (Fig. 5). Aneurysms arising from the carotid siphon or from the anterior communicating artery usually appear as round lesions, hypointense on T2WI because of flow void. Partially thrombosed aneurysm in the sellar region can show high signal intensity on T1WI [46]. Thus, an imaging study should be completed with MR angiography, which is best with a contrast-enhanced technique, to exclude this pathology [25].

Rathke cleft cysts (RCCs) occur with T1 hyperintensity because of the variable protein content [56] (Fig. 6). RCC, which can be either intra- or suprasellar, is usually located along the midline and does not present a fluid debris level [40]. A hypointense intracystic nodule on T2WI, related to concretion of proteinaceous material within the RCC, is typical (Fig. 6c). The variable MRI appearance of RCC may cause difficulties in the differential diagnosis with PA. Moreover, a large suprasellar RCC may mimic PA even clinically, with acute onset of headache and visual deficit, as described by the recent work of Binning et al. [57].

Craniopharingioma is another pathology that can be difficult to distinguish from PA. It is usually an intra-/suprasellar lesion with variable solid, cystic and calcified components [40, 58]. The cystic component may contain a proteinaceous fluid, appearing hyperintense on T1WI, and mimicing haemorrhagic degeneration. Careful evaluation of T2WI together with the acquisition of a CT scan to rule out calcific components can help to obtain the correct diagnosis [40].

Other conditions that can simulate PA on imaging are lipoma, dermoid cysts and postoperative changes. Lipoma and dermoid cysts contain fat and can be confirmed with fat-suppressed images. Anyway, these pathologies do not usually appear with the clinical syndrome of PA.