British Journal of Neurosurgery, April 2015; 29(2): 303–305 © 2014 The Neurosurgical Foundation ISSN: 0268-8697 print / ISSN 1360-046X online DOI: 10.3109/02688697.2014.969681
Delayed pan-hypopituitarism as a complication following endovascular treatment of bilateral internal carotid artery aneurysms. A case report and review Jonathan Hall1, Carmela Caputo2, Carlos Chung1, Michael Holt3 & Yi Yuen Wang1,4 1Department of Neurosurgery, St Vincent ’s Hospital, Fitzroy, Victoria, Australia, 2Department of Endocrinology, St Vincent ’s
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Hospital, Fitzroy, Victoria, Australia, 3Department of Radiology, St Vincent’s Hospital, Fitzroy, Victoria, Australia, and 4Department of Surgery, The University of Melbourne, St Vincent ’s Hospital, Fitzroy, Victoria, Australia
for the insertion of the flow-diverting stent. In addition to the aspirin, clopidogrel 75 mg daily was started 1 week prior to insertion of the flow-diverting stent for the left cavernous aneurysm. Dual antiplatelet was maintained for 3 months after which clopidogrel was ceased and aspirin continued. No peri-procedural complications were encountered. Follow-up MRI scan 1 year after stenting demonstrated significant reduction in size of the left cavernous aneurysm and occlusion of the right cavernous/supraclinoid aneurysm. However, 18 months following deployment of the flow-diverting stent, the patient presented with a 2-week history of headache, lethargy, nausea, vomiting and diarrhoea. During investigations she was found to be hyponatraemic and hypopituitary with a random cortisol of 9 nmol/L, T4 of 8 pmol/L and an elevated prolactin level suggestive of a stalk effect (Table I). Hormone replacement with corticosteroid and thyroid hormone was commenced with resolution of her headaches, lethargy, nausea, vomiting and diarrhoea. MRI at this point revealed slight expansion of the coil mass within the right cavernous aneurysm with compression and displacement of the pituitary gland to the left (Fig. 2). Regular outpatient monitoring of both her pituitary function and aneurysm status has been continued with MRI/A imaging. She remains on replacement hydrocortisone of 16 mg mane and 6 mg nocte and thyroxine 75 mg daily and continues to take aspirin 100 mg.
Abstract Pan-hypopituitarism has been reported in patients who are subsequently found to have a cerebral aneurysm and there have been reports of pituitary dysfunction immediately following both surgical and endovascular treatment. The authors report a rare case of delayed pan-hypopituitarism following endovascular treatment of bilateral internal carotid artery aneurysms with coil embolisation and flow-diverting stents. Keywords: endovascular; internal carotid artery aneurysm; hypopituitarism
Case report A 50-year-old female presented to her General Practitioner with persistent headaches. Physical examination showed normal cranial nerve examination. Serum biochemistry revealed no abnormalities. Cranial imaging performed included a computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain demonstrating bilateral internal carotid artery (ICA) aneurysms extending posteriorly into the suprasellar cistern with compression of the pituitary gland. A catheter digital subtraction cerebral angiogram confirmed a left cavernous aneurysm (Fig. 1A) and a right cavernous/supraclinoid aneurysm (Fig. 1B). Her pituitary function prior to intervention revealed no abnormality (Table I) and she subsequently underwent balloon-assisted deployment of a total of 11 coils, a combination of HydroCoils (MicroVention Terumo, Aliso Viejo, California) and Baer 360 GDC platinum coils to the right cavernous/supraclinoid aneurysm. Treatment of the left cavernous aneurysm took place 3 months later with deployment of a 4 ⫻ 25 mm SILK flow-diverting stent. Both procedures were uncomplicated. Aspirin 100 mg was used following balloon-assisted coiling of the right-sided aneurysm and this was continued
Discussion Pituitary dysfunction is estimated to have an annual incidence of 4.2 cases per 100,000 and a prevalence of 45.5 cases per 100,000. Cerebral aneurysm is an uncommon cause of this dysfunction and may account for less than 0.2% of cases.1 In particular, cavernous aneurysms may be responsible for pituitary dysfunction by localised mass effect or by
Correspondence: Jonathan Hall, Department of Neurosurgery, St Vincent’s Hospital, 5th Floor, Daly Wing, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia. Tel: ⫹ 61 392 882 211. E-mail address: [email protected] Received for publication 28 February 2014; accepted 21 September 2014
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Fig. 1. (A) DSA 3D reconstruction showing a 11.7 ⫻ 11.8 mm left cavernous aneurysm pointing postero-medially and extending into the subarachnoid space; (B) DSA 3D reconstruction showing a right 11.3 ⫻ 16.4 mm cavernous/supraclinoid aneurysm pointing postero-medially.
vascular compromise. Rarely, pituitary hypofunction has been reported immediately following both endovascular and surgical treatment of cerebral aneurysms. Pituitary dysfunction can be the result of mass effect or vascular compromise and ischaemia. The most common cause of hypopituitarism is mass effect secondary to tumours, both pituitary and non-pituitary. Pituitary adenomas are recognised as the most common cause of hypopituitarism2; however, a large number of non-pituitary tumours, such as craniopharyngiomaa, meningiomas, gliomas, chordomas, and metastases, are also well-recognised causes of extrinsic compression of the pituitary gland and stalk resulting in pituitary dysfunction. The pituitary hormones display varying degrees of sensitivity to compression, resulting in underproduction, with growth hormone being most sensitive followed by the gonadotropins, thyroid-stimulating hormone, and adrenocorticotropic hormone. Pituitary stalk compression, conversely, often results in increased secretion of prolactin due to loss of inhibitory control. In all, tumours account for up to 70% of all causes of pituitary dysfunction. Aneurysms have also been shown to cause hypopituitarism through direct mass effect on pituitary stalk; these are usually large cavernous or proximal supraclinoid ICA aneuryms or bilateral aneurysms.
Ischaemia of the pituitary, secondary to traumatic brain injury, subarachnoid haemorrhage, carotid dissection or other rare causes such as Sheehan’s syndrome may also result in hypopituitarism. The arterial supply to the pituitary comes from an anastomotic network formed by the superior hypophyseal arteries from the supraclinoid ICA, inferior hypophyseal arteries and the capsular arteries of McConnell from the cavernous ICA. These small vessels are particularly vulnerable damage following subarachnoid haemorrhage and traumatic brain injury. Haemorrhages, necrosis and fibrosis of the pituitary have all been demonstrated following these injuries.2 It is feasible that incorporation of flowdiverting stents into the vascular endothelium over time may potentially compromise flow in these small vessels, resulting in ischaemia of the pituitary gland. Indeed, delayed ischaemic complications following intra-cranial stent deployment have been reported at 23 months.3 The pituitary gland in this case was particularly at risk as there were pathologies bilaterally on the ICAs with mass effect exerted from the right and potential ischaemia from the left.
Table I. Pituitary function: (A) pre-aneurysm treatment; (B) 18 months post stent deployment; (C) post hormone replacement. Hormonal test (A) (B) (C) Range 8am cortisol (nmol/L) Random cortisol (nmol/L) ACTH (ng/L) IGF-1 (nmol/L) TSH (uU/mL) fT4 (pmol/L) fT3 (pmol/L) Prolactin (mIU/L) LH (IU/L) FSH (IU/L Oestradiol (pmol/L) Na (mmol/L)
1.08 15 298 4.2 7.6 493 138
36 9 ⬍5 6 1.33 8 3.7 3822 0.6 2.8 ⬍ 50 117
946 8 19.5 ⬍ 0.01 20 5.0 2576 0.1 0.4 ⬍ 50 140
* ⬍ 46 11–31 0.35–4.94 9–19 2.6–5.7 110–560 ⫹ # ^ 135–145
*Ref range: 0900: 100–535, 1600: 80–450. ⫹Ref range: follicular 2.4–6.6, mid cycle 9.1–74, luteal ⬍ 9.3, post-menopausal ⬎ 10.0. #Ref range: follicular 3.0–8.1, mid cycle 2.6–16.7, luteal 1.4–5.5, postmenopausal ⬎ 27.0. ^Ref range: follicular 80–920, luteal 80–1150, peri-ovulatory (⫾ 3 days) 140–2380 post-menopausal ⬎ 100.
Fig. 2. T1 weighted coronal MRI demonstrating hydrocoil mass (straight white arrow) expanding the right cavernous sinus with displacement and compression of the pituitary gland to the left (curve white arrow).
Panhypopituitarism following endovascular treatment of aneurysms 305 It is postulated that the hypopituitarism observed in this case was as a result of a combination of mass effect exerted by the coiled mass of the right ICA aneurysm and with compromise to the blood supply of the pituitary gland as a result of the flow-diverting stent to the left ICA. The extended time course for the development of pituitary dysfunction in this case could be due to gradual occlusion and subsequent vascular compromise of the perforating vessels. The HydroCoils are designed to increase in mass once deployed and could also account for a slow subtle deformation of the pituitary and pituitary stalk and subsequent pituitary dysfunction. In this case, it is difficult to fully delineate the cause of the pituitary dysfunction due to artefact from the coils and stent.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Conclusion We report a delayed complication following hybrid endovascular treatment of bilateral cavernous aneurysms resulting in pituitary dysfunction. The patient developed this complication some 18 months following endovascular stenting and
coiling, most likely due to a combination of mass effect and ischaemia to the pituitary gland. A raised index of clinical suspicion for this phenomenon and the routine testing of pituitary function in all patients who undergo treatment of bilateral cavernous and supraclinoid aneurysms with flow diverters should be employed. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Orozco LD, Buciuc RF. Balloon-assisted coiling of the proximal lobule of a paraophthalmic aneurysm causing panhypopituitarism: technical case report. Surg Neurol Int 2011;2:59. 2. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK , Ghigo E. Hypopituitarism. Lancet 2007;369:1461–70. 3. Fiorella D, Hsu D, Woo HH, Tarr RW, Nelson PK . Very late thrombosis of a pipeline embolization device construct: case report. Neurosurgery. 2010;67:onsE313-4; discussion onsE4.
Delayed pan-hypopituitarism as a complication following endovascular treatment of bilateral internal carotid artery aneurysms. A case report and review Jonathan Hall1, Carmela Caputo2, Carlos Chung1, Michael Holt3 & Yi Yuen Wang1,4 1Department of Neurosurgery, St Vincent ’s Hospital, Fitzroy, Victoria, Australia, 2Department of Endocrinology, St Vincent ’s
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Hospital, Fitzroy, Victoria, Australia, 3Department of Radiology, St Vincent’s Hospital, Fitzroy, Victoria, Australia, and 4Department of Surgery, The University of Melbourne, St Vincent ’s Hospital, Fitzroy, Victoria, Australia
for the insertion of the flow-diverting stent. In addition to the aspirin, clopidogrel 75 mg daily was started 1 week prior to insertion of the flow-diverting stent for the left cavernous aneurysm. Dual antiplatelet was maintained for 3 months after which clopidogrel was ceased and aspirin continued. No peri-procedural complications were encountered. Follow-up MRI scan 1 year after stenting demonstrated significant reduction in size of the left cavernous aneurysm and occlusion of the right cavernous/supraclinoid aneurysm. However, 18 months following deployment of the flow-diverting stent, the patient presented with a 2-week history of headache, lethargy, nausea, vomiting and diarrhoea. During investigations she was found to be hyponatraemic and hypopituitary with a random cortisol of 9 nmol/L, T4 of 8 pmol/L and an elevated prolactin level suggestive of a stalk effect (Table I). Hormone replacement with corticosteroid and thyroid hormone was commenced with resolution of her headaches, lethargy, nausea, vomiting and diarrhoea. MRI at this point revealed slight expansion of the coil mass within the right cavernous aneurysm with compression and displacement of the pituitary gland to the left (Fig. 2). Regular outpatient monitoring of both her pituitary function and aneurysm status has been continued with MRI/A imaging. She remains on replacement hydrocortisone of 16 mg mane and 6 mg nocte and thyroxine 75 mg daily and continues to take aspirin 100 mg.
Abstract Pan-hypopituitarism has been reported in patients who are subsequently found to have a cerebral aneurysm and there have been reports of pituitary dysfunction immediately following both surgical and endovascular treatment. The authors report a rare case of delayed pan-hypopituitarism following endovascular treatment of bilateral internal carotid artery aneurysms with coil embolisation and flow-diverting stents. Keywords: endovascular; internal carotid artery aneurysm; hypopituitarism
Case report A 50-year-old female presented to her General Practitioner with persistent headaches. Physical examination showed normal cranial nerve examination. Serum biochemistry revealed no abnormalities. Cranial imaging performed included a computed tomography (CT) scan and magnetic resonance imaging (MRI) of the brain demonstrating bilateral internal carotid artery (ICA) aneurysms extending posteriorly into the suprasellar cistern with compression of the pituitary gland. A catheter digital subtraction cerebral angiogram confirmed a left cavernous aneurysm (Fig. 1A) and a right cavernous/supraclinoid aneurysm (Fig. 1B). Her pituitary function prior to intervention revealed no abnormality (Table I) and she subsequently underwent balloon-assisted deployment of a total of 11 coils, a combination of HydroCoils (MicroVention Terumo, Aliso Viejo, California) and Baer 360 GDC platinum coils to the right cavernous/supraclinoid aneurysm. Treatment of the left cavernous aneurysm took place 3 months later with deployment of a 4 ⫻ 25 mm SILK flow-diverting stent. Both procedures were uncomplicated. Aspirin 100 mg was used following balloon-assisted coiling of the right-sided aneurysm and this was continued
Discussion Pituitary dysfunction is estimated to have an annual incidence of 4.2 cases per 100,000 and a prevalence of 45.5 cases per 100,000. Cerebral aneurysm is an uncommon cause of this dysfunction and may account for less than 0.2% of cases.1 In particular, cavernous aneurysms may be responsible for pituitary dysfunction by localised mass effect or by
Correspondence: Jonathan Hall, Department of Neurosurgery, St Vincent’s Hospital, 5th Floor, Daly Wing, 41 Victoria Parade, Fitzroy, Victoria 3065, Australia. Tel: ⫹ 61 392 882 211. E-mail address: [email protected] Received for publication 28 February 2014; accepted 21 September 2014
303
304
J. Hall et al.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Fig. 1. (A) DSA 3D reconstruction showing a 11.7 ⫻ 11.8 mm left cavernous aneurysm pointing postero-medially and extending into the subarachnoid space; (B) DSA 3D reconstruction showing a right 11.3 ⫻ 16.4 mm cavernous/supraclinoid aneurysm pointing postero-medially.
vascular compromise. Rarely, pituitary hypofunction has been reported immediately following both endovascular and surgical treatment of cerebral aneurysms. Pituitary dysfunction can be the result of mass effect or vascular compromise and ischaemia. The most common cause of hypopituitarism is mass effect secondary to tumours, both pituitary and non-pituitary. Pituitary adenomas are recognised as the most common cause of hypopituitarism2; however, a large number of non-pituitary tumours, such as craniopharyngiomaa, meningiomas, gliomas, chordomas, and metastases, are also well-recognised causes of extrinsic compression of the pituitary gland and stalk resulting in pituitary dysfunction. The pituitary hormones display varying degrees of sensitivity to compression, resulting in underproduction, with growth hormone being most sensitive followed by the gonadotropins, thyroid-stimulating hormone, and adrenocorticotropic hormone. Pituitary stalk compression, conversely, often results in increased secretion of prolactin due to loss of inhibitory control. In all, tumours account for up to 70% of all causes of pituitary dysfunction. Aneurysms have also been shown to cause hypopituitarism through direct mass effect on pituitary stalk; these are usually large cavernous or proximal supraclinoid ICA aneuryms or bilateral aneurysms.
Ischaemia of the pituitary, secondary to traumatic brain injury, subarachnoid haemorrhage, carotid dissection or other rare causes such as Sheehan’s syndrome may also result in hypopituitarism. The arterial supply to the pituitary comes from an anastomotic network formed by the superior hypophyseal arteries from the supraclinoid ICA, inferior hypophyseal arteries and the capsular arteries of McConnell from the cavernous ICA. These small vessels are particularly vulnerable damage following subarachnoid haemorrhage and traumatic brain injury. Haemorrhages, necrosis and fibrosis of the pituitary have all been demonstrated following these injuries.2 It is feasible that incorporation of flowdiverting stents into the vascular endothelium over time may potentially compromise flow in these small vessels, resulting in ischaemia of the pituitary gland. Indeed, delayed ischaemic complications following intra-cranial stent deployment have been reported at 23 months.3 The pituitary gland in this case was particularly at risk as there were pathologies bilaterally on the ICAs with mass effect exerted from the right and potential ischaemia from the left.
Table I. Pituitary function: (A) pre-aneurysm treatment; (B) 18 months post stent deployment; (C) post hormone replacement. Hormonal test (A) (B) (C) Range 8am cortisol (nmol/L) Random cortisol (nmol/L) ACTH (ng/L) IGF-1 (nmol/L) TSH (uU/mL) fT4 (pmol/L) fT3 (pmol/L) Prolactin (mIU/L) LH (IU/L) FSH (IU/L Oestradiol (pmol/L) Na (mmol/L)
1.08 15 298 4.2 7.6 493 138
36 9 ⬍5 6 1.33 8 3.7 3822 0.6 2.8 ⬍ 50 117
946 8 19.5 ⬍ 0.01 20 5.0 2576 0.1 0.4 ⬍ 50 140
* ⬍ 46 11–31 0.35–4.94 9–19 2.6–5.7 110–560 ⫹ # ^ 135–145
*Ref range: 0900: 100–535, 1600: 80–450. ⫹Ref range: follicular 2.4–6.6, mid cycle 9.1–74, luteal ⬍ 9.3, post-menopausal ⬎ 10.0. #Ref range: follicular 3.0–8.1, mid cycle 2.6–16.7, luteal 1.4–5.5, postmenopausal ⬎ 27.0. ^Ref range: follicular 80–920, luteal 80–1150, peri-ovulatory (⫾ 3 days) 140–2380 post-menopausal ⬎ 100.
Fig. 2. T1 weighted coronal MRI demonstrating hydrocoil mass (straight white arrow) expanding the right cavernous sinus with displacement and compression of the pituitary gland to the left (curve white arrow).
Panhypopituitarism following endovascular treatment of aneurysms 305 It is postulated that the hypopituitarism observed in this case was as a result of a combination of mass effect exerted by the coiled mass of the right ICA aneurysm and with compromise to the blood supply of the pituitary gland as a result of the flow-diverting stent to the left ICA. The extended time course for the development of pituitary dysfunction in this case could be due to gradual occlusion and subsequent vascular compromise of the perforating vessels. The HydroCoils are designed to increase in mass once deployed and could also account for a slow subtle deformation of the pituitary and pituitary stalk and subsequent pituitary dysfunction. In this case, it is difficult to fully delineate the cause of the pituitary dysfunction due to artefact from the coils and stent.
Br J Neurosurg Downloaded from informahealthcare.com by Nyu Medical Center on 04/25/15 For personal use only.
Conclusion We report a delayed complication following hybrid endovascular treatment of bilateral cavernous aneurysms resulting in pituitary dysfunction. The patient developed this complication some 18 months following endovascular stenting and
coiling, most likely due to a combination of mass effect and ischaemia to the pituitary gland. A raised index of clinical suspicion for this phenomenon and the routine testing of pituitary function in all patients who undergo treatment of bilateral cavernous and supraclinoid aneurysms with flow diverters should be employed. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Orozco LD, Buciuc RF. Balloon-assisted coiling of the proximal lobule of a paraophthalmic aneurysm causing panhypopituitarism: technical case report. Surg Neurol Int 2011;2:59. 2. Schneider HJ, Aimaretti G, Kreitschmann-Andermahr I, Stalla GK , Ghigo E. Hypopituitarism. Lancet 2007;369:1461–70. 3. Fiorella D, Hsu D, Woo HH, Tarr RW, Nelson PK . Very late thrombosis of a pipeline embolization device construct: case report. Neurosurgery. 2010;67:onsE313-4; discussion onsE4.
