Aneurysmal subarachnoid haemorrhage in the pituitary fossa of a patient with acromegaly – a rare phenomenon

Background

The pituitary fossa is an important structure that encloses and protects the pituitary gland. The sella turcica, a depression in the sphenoid bone, forms the floor of the fossa (1). Superiorly, the roof of the fossa is composed of the diaphragma sellae (an extension of the dura) and a subdiaphragmatic cistern. This cistern represents a space situated between the arachnoid mater and the pia mater, filled with cerebrospinal fluid (CSF), and through which CSF circulates (2). The subdiaphragmatic cistern communicates with the chiasmatic cistern which lies above the diaphragma, which in turn connects to the lamina terminalis and carotid cisterns (2). Within the fossa, the fibrous capsule of the pituitary separates the gland from the contents of the cavernous sinus laterally (3). The anatomical and histological features of the fossa walls can, however, vary – resulting in inconsistencies in the nature and integrity of the sella barrier (4). Abnormal intrasellar findings include benign masses such as pituitary adenomas, non-pituitary tumours such as craniopharyngiomas, malignant lesions such as pituitary carcinoma, metastases, germ cell tumours and lymphoma. Non-neoplastic conditions include hypophysitis, cysts and vascular lesions (5). Spontaneous haemorrhage in the fossa typically occurs in the setting of a pre-existing intrasellar pathology. We describe a unique case of an extrasellar subarachnoid haemorrhage (SAH) identified communicating with the pituitary fossa.

Case presentation

The patient was a 65-year-old male who had a prior diagnosis of acromegaly made 24 years previously. The initial diagnosis of acromegaly had been made in 1997 (age 41) after presentation with pituitary apoplexy; sudden severe headache and visual disturbance in a patient with notable coarse facial features, prognathism, macroglossia and acral enlargement. The diagnosis was confirmed by a significantly elevated plasma growth hormone (GH) of 58.5 mIU/L (reference range (RR): 0–15) and insulin-like growth factor (IGF1) level of 89 nmol/L (RR: 11-37). Magnetic resonance imaging (MRI) demonstrated a pituitary macroadenoma with suprasellar extension, optic chiasm compression (Fig. 1A) and extensive areas of necrosis without haemorrhage in the gland (hypointense on T1 and hyperintense on T2). He underwent transsphenoidal decompression of the pituitary lesion, with subsequent normalization of visual fields and acuity. Histopathology assessment confirmed a pituitary adenoma displaying positive immunostaining for GH and prolactin. Postoperatively he had residual tumour within the fossa and persistently elevated plasma IGF1 and GH levels. He was started on somatostatin analogue treatment, but this was soon discontinued due to severe gastrointestinal side effects. He underwent fractionated external beam radiation therapy (45 Gy in 25 fractions) and subsequently developed panhypopituitarism requiring hormone replacement with prednisolone, thyroxine and testosterone. IGF1 levels remained persistently elevated but were normalized after the commencement of cabergoline (CAB) 1 mg twice weekly. MRI up to 18 years after radiotherapy showed an expanded and largely empty pituitary fossa, with a small amount of residual tumour tissue situated in its posterior aspect (Fig. 1B–D). After many years of clinical stability, he failed to return to the clinic and was lost to follow-up for a further period.

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(A) Coronal section of MRI in 1997 demonstrating a 3.6 cm × 2.4 cm × 3.5 cm pituitary macroadenoma at initial presentation, with suprasellar extension, compression of the optic chiasm on the right and left cavernous sinus invasion. (B) Sagittal T1 MRI image in 2016 showing an enlarged and mostly empty sella with residual tumour in the posterior aspect of the fossa. (C) Coronal T1 image in 2016 showing an enlarged and mostly empty sella with residual tumour in the posterior aspect of the fossa. (D) Coronal T2 MRI image in 2016 showing an enlarged and mostly empty sella with residual tumour in the posterior aspect of the fossa.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 1; 10.1530/EDM-22-0363

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In 2021, at the age of 65, he presented to the Emergency Department of another hospital with a 5-day history of worsening severe headaches, photophobia and vomiting. He was hypertensive (156/88 mmHg) on the background of a known history of hypertension, but other vital signs were normal. Glasgow Coma Scale was 14/15 due to confusion. Ocular examination showed right eye ptosis but normal ocular motion and pupillary responses. There were no other focal neurological deficits.

Investigation

Urgent computed tomography (CT) scanning revealed hyperdensity along bilateral sylvian fissures, in the interhemispheric fissure and in bilateral parafalcine regions, consistent with SAH. Interestingly, another area of hyperdensity was observed within the widened sella, raising the possibility another episode of pituitary apoplexy. Biochemical investigations revealed a mildly elevated IGF1 of 35.2 nmol/L (RR: 6.3–28.1), GH 6.8 mIU/L (RR: 0-15), thyroid-stimulating hormone <0.01 mIU/L (RR: 0.40–4.00), free thyroxine 13.2 pmol/L (RR: 9-19), free tri-iodothyronine 3.0 pmol/L (RR: 2.6–6.0), cortisol 379 nmol/L (RR: 100–540) after a dose of hydrocortisone, total testosterone >52 nmol/L (RR: 10.0–30.0) a few weeks after i.m. testosterone administration and prolactin < 25mIU/L (RR: <400). Further characterization of the pituitary fossa with MRI showed a 14 × 16 × 11 mm area of mild T1 hyperintensity and T2 hypodensity within the expanded sella, corresponding to the area of hyperdensity on CT imaging (Fig. 2C–E). There was no post-contrast enhancement. This lesion was separate to the residual tumour indicating an extra-tumoural bleed. Acute haemorrhage in the anterior hemispheric and bilateral sylvian fissures was again noted.

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(A) Subarachnoid haemorrhage seen in the sylvian fissures on axial CT view. (B) Axial CT view showing hyperdensity within the sella, representing haemorrhage. (C) Sagittal image in 2020, after presentation with SAH, showing hyperintensity (green arrow) in the sella. This lesion is separate from the residual pituitary tumour (orange arrow) at the bottom of the pituitary fossa. (D) Coronal T1 image in 2020, after presentation with SAH, showing hyperintensity in the sella. (E) Coronal T2 showing hypointensity in expanded sella.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 1; 10.1530/EDM-22-0363

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Outcome and follow-up

A right frontal external ventricular drain was inserted in view of imaging signs of hydrocephalus. Angiography demonstrated a distal anterior cerebral artery aneurysm. He underwent urgent left frontal craniotomy and clipping of the aneurysm which was complicated by postoperative anterior cerebral artery spasm and a lacunar infarct involving the lateral aspect of the genu of the corpus callosum. His recovery was further complicated by aspiration pneumonia, and a temporary tracheostomy was required due to long ventilatory wean. However, he was discharged home after admission of 32 days and eventually made a full recovery. Repeat MRI at 3 months post-discharge had reverted to the previous appearance of an empty sella with residual tumour tissue but no haemorrhagic focus (Fig. 3). He remained on his usual pituitary hormonal replacement. His plasma IGF1 level rose to 98 nmol/L (RR: 8–30) during the hospital admission because of the temporary discontinuation of CAB treatment, but it later normalized with the recommencement of dopamine agonist therapy (Table 1).

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(A) Sagittal T1 image 3 months after SAH, demonstrating resolution of haemorrhage. (B) Coronal T1 image 3 months after SAH, demonstrating resolution of haemorrhage.

Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 1; 10.1530/EDM-22-0363

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Discussion

This case illustrates the complex anatomical relationship of the contents of the pituitary fossa with the subarachnoid space and its disruption in the presence of intra-sella pathology. Although the normal anatomy of the roof of the fossa is variable and inconsistently described in the literature, it is widely accepted that CSF is confined to subarachnoid space and does not circulate freely in the pituitary fossa. Anatomical studies have demonstrated the presence of arachnoid membrane and trabeculae within a subdiaphragmatic cistern located in the pituitary fossa (2). Intraoperative and radiological studies have concluded that the tumour–CSF interface, which is composed of the arachnoid layer and/or dura mater and/or a pituitary adenoma, influences of risk an intraoperative CSF fistula formation (6).

Our case is unusual in that pooling of aneurysmal blood from the subarachnoid space into the pituitary fossa mimicked the radiological appearance of pituitary apoplexy, in the absence of any pituitary haemorrhage or new intrasellar pathology. This is a rare phenomenon that has not been reported in the literature. From a neuroanatomical perspective, its occurrence is, however, conceivable. We speculate that the combination of past tumour invasion, a weak sellar barrier and surgical manipulation would have led to the disruption of the normal roof of the fossa, thereby allowing later collection of SAH in the sella, possible through the suprasellar cistern (7). Moreover, the presence of subarachnoid blood within the fossa further consolidates the notion that intrasellar arachnoid tissue can exist within a subdiaphragmatic cistern as a normal anatomical variant (2). The clinical challenge is distinguishing an apoplectic pituitary tumour from an extra-tumoral haemorrhage. This case exemplifies how careful radiological evaluation is necessary to delineate the two entities and emphasizes the importance of serial imaging to depict the eventual resolution of haematoma adjacent to residual tumours.

Further, this case raises the association between SAH and pituitary apoplexy. A well-described causal relation is non-aneurysmal SAH arising as a manifestation of pituitary apoplexy. Extravasation of haemorrhagic components from the pituitary into the subarachnoid space produces the typical clinical characteristics of SAH. Initial investigations can be non-discriminatory as imaging with CT or MRI usually demonstrates blood in the subarachnoid space and CSF analysis may reveal erythrocytes and/or xanthochromia (8). The MRI appearances of the adenoma may suggest fresh haemorrhage (hyperintense intratumoral lesion with gadolinium on T1-weighted image), and angiographic studies are required to exclude a ruptured intracranial aneurysm and to initiate urgent surgical decompression of the pituitary mass. Conversely, aneurysmal SAH likely preceding pituitary apoplexy has also been reported (9, 10). Compromised tumour perfusion secondary to post-haemorrhagic vasospasm or direct vascular compression from an aneurysm is a possible contributor to the sequela of pituitary adenoma infarction. Other potential but uncommon causes of SAH in the context of a pituitary adenoma are intraoperative rupture of an undiagnosed aneurysm, accidental injury to the internal carotid artery during tumour resection or spontaneous intratumoral aneurysm rupture (11, 12).

Finally, our case provides supporting evidence for the previously reported association of cerebral aneurysms with acromegaly, possibly related to active GH hypersecretion. In their study of patients with GH-secreting adenomas, Manara et al. observed that 17.3% of patients harboured one or more intracranial aneurysms (13). In a different series of 208 acromegalic patients, when confounders such as previous neurosurgery and radiation were accounted for by reviewing preoperative imaging, 4.3 % were found to have cerebral aneurysms. This prevalence was still significantly greater than in a control population (14). Many investigators have shown that elevated IGF1 and GH levels can induce vascular endothelial abnormalities, hypothetically predisposing to the formation of aneurysms (15). We suspect that many years of active disease in our patient could have led to endothelial dysfunction and aneurysm development, although de novo aneurysm formation after previous radiation therapy is also an important entity to be considered in this case. Over 50 cases of cerebral aneurysms, occurring after radiotherapy for brain tumours and often presenting with SAH, have been reported in the literature (16).

Conclusion

This is the first reported case of aneurysmal SAH pooling in the pituitary fossa and mimicking pituitary apoplexy on CT imaging. This phenomenon was possible due to communication between the subarachnoid space and a largely empty sella in a patient with a previous macroadenoma treated with surgical resection and radiotherapy. MRI outlined the presence of blood within the pituitary fossa, clearly differentiating SAH from haemorrhagic pituitary apoplexy.

Declaration of interest

There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Funding

This study did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Patient consent

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.

Author contribution statement

P.F wrote the manuscript. M.M is the treating physician and contributed to the case description and discussion. Both authors reviewed the manuscript.