Endocrine Caredoi: 10.4183/aeb.2014.53

53

Acta Endocrinologica (Buc), vol. X, no. 1, p. 53-64, 2014

*Correspondence to: Daniel Ilie Rotariu MD, “N. Oblu” Emergency Hospital - Neurosurgery, No. 2 Ateneului Street, Iasi, 700309, Romania, E-mail: dr_rotariu@yahoo.co.uk

Abstract Introduction. The aim of this study is to appreciate the visual and endocrine outcome and to determine the factors that may influence the outcome of patients with pituitary apoplexy. Material and Methods. Between January 2006 and March 2012, 81 pituitary tumors were treated at “N. Oblu” Clinical Emergency Hospital in Iasi. Investigations of 22 of these cases met the criteria for pituitary apoplexy (17 cases of non-secreting pituitary adenomas and 5 cases of secreting tumors (4 GH secreting adenomas with acromegaly and 1 prolactinoma). Twenty one patients underwent surgery. The mean follow-up duration was 21 months. Results. Distribution between sexes was 1:1, with a mean age of 55.0 years. In all cases pituitary apoplexy emerged in patients with macroadenomas (>1cm). 77.27% presented decreased visual acuity, cranial nerve palsy was found in 45.45%. Visual acuity improved after surgical decompression best results being obtained in patients operated within first 7 days from onset (p=0.005); 80% recovered the CN palsy after surgery (p=0.005), with no relation to delay of surgery (p=0.26) or cavernous sinus invasion (0.095); 18.18% presented with

pituitary deficiency and maintained it after surgery, the rate of new pituitary deficiency was 27.77% significantly higher in patients operated using craniotomies (p=0.001). Conclusions. Clinical apoplexy emerged in patients with macroadenomas unrelated to the tumor type. Early surgical decompression (< 7 days) and high dose corticoids represent the main therapeutic approach for obtaining good recovery of visual function. CN palsy has a good prognostic not being related to the delay of surgery. Pituitary dysfunction at presentation is irreversible and has a high occurrence after surgical decompression, requiring lifelong hormone replacement.

Key words: pituitary apoplexy, pituitary adenoma, pituitary deficiency.

IntRoduCtIon

Pituitary apoplexy (PA) represents the most severe complication of pituitary adenomas and consists of a clinical syndrome characterized by sudden onset of symptoms, headache with visual impairment, ophthalmoplegia, hypopituitarism and altered level of

PItuItARy APoPlexy MAnAgeMent And CondItIonIng fACtoRs of outCoMe

D.I. Rotariu1,*, Z. Faiyad2, S. Gaivas3, B.F. Iliescu2, I. Poeata1

1“Gr.T.Popa” University of Medicine and Pharmacy - Neurosurgery, 2“N. Oblu” Clinical Emergency Hospital - Neurosurgery, Iasi, Romania 3Marienhaus Klinikum

Bendorf - Neurosurgery, Waldbreitbach, Neuwied, Germany

D.I. Rotariu et al.

54

consciousness to coma (1, 2). PA appears when acute haemorrhage or infarction emerge in a pre-existing pituitary adenoma (1, 3-5). The pathophysiology of PA is not completely understood and this leads to several theories including: 1. Tumour enlargement with outgrowing of blood supply resulting in ischemic necrosis with secondary haemorrhage (6); a second theory postulates that compression of the vascular supply, superior hypophyseal artery over the diaphragma sellae by the upward growth of the tumour, produces necrosis in both tumour and pituitary gland (7), and the third theory suggests that critical perfusion pressure of pituitary adenomas is below the normal arterial pressure and sudden modification in perfusion pressure prones to adenoma infarction (8). The clinical syndrome is the consequence of sudden increase of the sella turcica content, with compression of the adjacent vascular and nervous structures from the suprasellar area. Compression of the optic chiasm/optic nerves results in a decrease of visual acuity (VA) and various visual field (VF) defects, but typically bi-temporal hemianopia, while compression of the structures from parasellar area, cavernous sinus, results in ophthalmoplegia and eyelid ptosis due to the compression of the 3rd, most common, 4th and 6th cranial nerves at this level (1, 2, 4, 9). It is important to make a clear distinction between patients with clinical symptoms of pituitary apoplexy and patients with pituitary adenomas that are asymptomatic and in whom the MRI exam shows isolated areas of haemorrhage or infarction (5, 10-12). Those cases should not be considered

as PA, having a different prognostic and evolution. Usually, patients with PA were described as a single entity with no distinction between the anatomo-pathologic type, ischemic or hemorrhagic, until 1988 when Villiers described the ischemic entity of apoplexy and assumed that patients harbouring this subtype are having a less severe clinical syndrome and a more favourable outcome (10), confirmed by Semple et al. in 2005 in a series of 59 patients (13). It is the purpose of this study to try to establish a correlation between different parameters of PA (time from onset to treatment, degree of visual impairment, pituitary function on admission) and outcome.

MAteRIAls And Methods

We have reviewed retrospectively all cases of pituitary adenomas operated on at “Prof. N. Oblu” Clinical Emergency Hospital in Iasi, between Jan. 2007 and Mar. 2012. Operations were made by a single senior neurosurgeon (I.P.), both transcranial and transsphenoidal approaches being performed. The whole resected specimens were sent for histological examination. The histological examination was performed in the Department of neuropathology of the same hospital and the MRI images were reviewed by two senior neuroradiologists. We have included all patients that met the selection criteria in Table 1. All signs and symptoms were graded according to the clinical neurological examination at admission

Pituitary apoplexy

55

and included: cranial nerve palsy (3rd, 4th ,

6th), signs of hydrocephalus, altered level of consciousness, visual impairments (decreased visual acuity, visual field defects) and also the time interval from beginning of symptoms to presentation, and possible precipitating factors such as: infection, surgery, anticoagulant state, history of RXT, hormonal treatment, myocardial infarction, and the treatment with dopamine agonists. On the MRI images we have taken into account: tumour dimensions, identification of normal pituitary gland and local extension, which included superior extension into the 3rd ventricle using the Hardy grading scale (14), inferior extension into the sphenoid sinus and lateral extension into the cavernous sinuses. For appreciation of lateral extension we have used the Knosp grading scale (15) and the degree of internal carotid encasement. Endocrine evaluation included dosage of GH, PRL, ACTH, TSH, fT4 and free cortisol, using the immunoassays method, at admission and fT4 and free cortisol in the 3rd postoperative day. Visual evaluation included: determination of visual acuity, the decimal scale being used for quantification, evaluation of visual field defects using Goldman perimetry, pre

and postoperatively, at 7 days and at 1 month postop. The interval between admission and surgery, surgical type of decompression, intra and postoperative complications such as diabetes insipidus (DI), pituitary insufficiency were also recorded. The follow-up protocol included clinical follow-up at 1 month with ophthalmologic exam (visual acuity and perimetry) and endocrine evaluation (global function evaluation in order to assess hormone deficiency). At 3 months the follow-up consisted of the same exams as at 1 month and MRI evaluation of the sellar region. We classified recovery after PA taking into account the following parameters: visual function (visual acuity and visual field analyses) and endocrine status (hormone deficiency and need for substitution). Statistical analyses was performed using SPSS version 20.0.0, with a value of p<0.05 considered significant.

Results

A number of 81 consecutive cases of pituitary adenomas were analyzed and 22 met the criteria for PA and were included in our study. Mean

Inclusion criteria exclusion criteriaAge more than 18 years Age less than 18 yearsPatient informed consent Previous surgery for pituitary adenoma

MRI evaluation preoperativePresence of pituitary tumour alone with no obvious clinical vidence of apoplexy

Clinic picture suggestive for pituitary apoplexy# Absence of MRI images

Table 1. Patient selection criteria

# sudden severe headache with or without nausea, vomiting/sudden deterioration of vision, including complete blindness (no light perception)/sudden cranial nerve palsies - third and sixth cranial nerve palsy.

D.I. Rotariu et al.

56

age was 55.0 years (21 to 82 years) with equal repartition between sexes (11 males and 11 females).

Presentation The mean length of time from onset of symptoms until presentation in the neurosurgery department was 11.7 days (3 to 45 days). Seventeen (77.2%) patients had no previous history of pituitary tumor or known endocrine dysfunction, one was known with a pituitary prolactinoma treated with Cabergolinum (Figure 1), and other four were found to have elevated GH levels at admission and presented the characteristic acromegaly stigmata (Figure 2), anyhow we were the first to diagnose their disease, so we considered them as newly diagnosed pituitary adenoma. Even in these cases the apoplexy was the event that determined their presentation. Dopamine agonist treatment (1 case), myocardial infarction (1 case) and infection (bacterial endocarditis) (1 case) were identified as precipitating factors in our series. Headache, usually with sudden onset, was the presenting symptom in 16 patients (72.7%), 2 patients (9%) were obnubilated and one was in coma. Seventeen patients (77%) presented with decreased VA and 2 of them had no

light perception (9%). VA was normal in 5 cases (23%). For a more accurate evaluation we classified decreased visual acuity in reduced but functional (VA > 0.1) in 9 patients (40.9%), reduced and not functional (counting fingers - CF, hand movements - HM, light perception - LP) in 5 cases (22.7%) and bilateral blindness in 2 cases (9%). VF analysis was available in 14 patients, 26.6% had normal VF (5 out of 14), 21.42% had bi-temporal hemianopia (3 patients) and 42.85% had other VF defects (scotoma/quadranopsy) (6 out of 14). In 8 patients VF assessment has not been performed because of low VA or altered level of consciousness. We have also evaluated the aspect of the optic discs and from 44 eyes 24 were normal, 12 had partial optic atrophy and 8 had total optic atrophy at fundoscopy. Ten patients (45.45%) presented with cranial nerve deficiency, 8 cases with 3rd nerve palsy, and two cases with 6th nerve palsy (Table 2).

Radiologic findings Radiological review of the cases showed that pituitary apoplexy in our series emerged in all cases with tumors larger than 10 mm (macro-adenomas), with a mean volume of 140 mm3 (Figs1, 2). Invasion of cavernous sinus was assessed using the Knosp classification

symptoms no. of cases %Headache 16 72%Decreased level of consciousness 2 9%Visual field defects*

- Bitemporal hemianopia- Irregular defects

936

60%33.33%66.66%

Decreased visual acuity 17 77%CN palsy 10 45%Pituitary deficiency 4 18%

Table 2. Symptomatology at presentation

* documented VF defects

Pituitary apoplexy

57

with the following results: Knosp 1 – 9.09% (2 cases), Knosp 2 – 31.81% (7 cases), Knosp 3 – 18.18% (4 cases) and Knosp 4 – 40.90%, (9 cases). The degree of carotid artery encasement was: 100% in 7 cases, 83.4% – 2 cases, 75% in 2 cases. The rest of the cases had a percent of carotid artery encasement under 50% (11 cases). The multivariate logistic regression of cranial nerve involvement showed a good correlation between the degree of ACI encasement, Knosp grade and cranial nerve involvement (p=0.05). The suprasellar extension was assessed using the Hardy classification: type I – 9 cases (41%), type II – 5 cases (22.7%),

type III – 4 cases (18.1%) and type IV – 4 cases (18.1%). The extension into the sphenoid sinus was observed in 4 cases (18%).

Endocrine evaluation All the patients had complete endocrine evaluation on admission and accordingly we had 17 cases of non-secreting pituitary adenomas and 5 cases of secreting tumors (4 GH secreting adenomas with acromegaly and 1 prolactinoma). The endocrine evaluation showed pituitary insufficiency (corticotroph and thyrotropic insufficiency) in 4 cases.

Figure 1. Case 1 – example of pituitary apoplexy in a patient treated with Cabergolinum® for a prolactin secreting adenoma. MR imaging at admission A- coronal section, expansive formation which occupies the sellar loge with extension to the left cavernous sinus (total encasement of the cavernous carotid artery), B-sagittal section - extension to the suprasellar region in the 3rd ventricle (type III) and sphenoid sinus. C, D MR imaging - 2 months postop subtotal resection, tumor at the level of left cavernous sinus. E –left 3rd nerve palsy at presentation, F – resolution of the cranial nerve deficit in the first day postop.

A B

C D

E F

D.I. Rotariu et al.

58

Treatment Twenty one patients underwent surgical decompression, the pterional

approach being used in 16 patients and the transsphenoidal in 5 patients. One case was managed conservatively.

Endocrine statusNon

secreting adenoma

Secreting adenomaTotal

GH PRL ACTH TSH Gonadotrope

17 4 1 0 0 0 22

Preoperative evaluation - Pituitary insufficiency

2 1 1 0 0 0 4

new postoperative deficit - Pituitary insufficiency - Diabetes insipidus

47

13

01

00

00

00

511

1 month evaluation - Pituitary insufficiency - Diabetes insipidus

51

11

11

00

00

00

73

Table 3. Endocrine status in patients with pituitary apoplexy

Figure 2. Case 2 – example of pituitary apoplexy in a patient with a relatively small GH secreting adenoma. MRI examination T1 + C shows mass lesion in the sellar fossa extending in the suprasellar cistern, the tumor is in contact with optic chiasm and the left carotid artery is encased in 62%, the tumor protrudes in the sphenoid sinus without invasion (A, B). MRI imaging at 3 months postop, gross total resection with preservation of normal pituitary gland (C, D). E and F pre and postop image showing the resolution of the cranial neuropathy after surgical intervention.

A B

C D

E F

Pituitary apoplexy

59

Pathologic findings The most common histological finding was hemorrhagic necrosis in 52.6% (10 out of 19), followed by infarction in 31.5% (6 cases) and hemorrhage in 15.7% (3 cases). In 3 cases the histology was not known (1 patient treated conservatively, results missing in 2 cases). Outcome The average length of follow- up in our series was 21 months (range 2 months – 5.2 yrs). The visual status at discharge was evaluated using visual acuity assessment. It was measured in 19 patients and it was normal (VA 1 for both eyes) in 9 patients (47.3%),

improved and useful but not normal – 7 patients (36.8%), improved but not useful in 2 (10.5%), unchanged in 1 (5.2%) (Table 4). In our series the outcome of the visual function was significantly improved after surgical intervention (p=0.001, Student T-test). However, we have divided the patients in 3 groups according to the delay of surgical intervention: Group 1, surgery < 7 days, Group 2, surgery between 7-14 days, and Group 3, surgery > 14 days. The best results were obtained for the Group 1. They had a significant amelioration in comparison with group 2 (p=0.005, Student T-test) and 3 (p=0.001, Student T-test), but we did not find statistically significant

Nr.crt.

Onset to Treatment

[days]

VA Preop

(OS/OD)

VA Postop

(OS/OD)

SuprasellarExtension*

VF Preop

VF Postop

(7th day)

VF 1

MO

CN Preop

CN Postop

Lateral Extension#

1 2 0.5/0.7 EXIT type II N N - N Exit KNOSP 22 4 NLP/0.1 HM/0.32 type IV - - - N N KNOSP 33 21 1.0/0.16 1.0/0.32 type II Q I I 3rd N KNOSP 44 60 HM/CF HM/0.1 type III Q Q I N N KNOSP25 14 CF/CF 0.2/0.25 type IV - - - 6th N KNOSP 3

6 7 NLP CF/0.25 type IV - - -3rd and

6th 6th KNOSP 3

7 4 0.1/NLP EXIT type IV - - - 3rd Exit KNOSP 38 14 0.25/1.0 1.0/1.0 type I S N N N N KNOSP 19 7 1.0/1.0 1.0/1.0 type I N N N 3rd N KNOSP 210 7 HM/CF HM/0.32 type III - - - N N KNOSP 411 60 0.32/0.5 0.4/0.5 type I Q I N N KNOSP 212 7 1.0/1.0 1.0/1.0 type I N N N N N KNOSP 213 10 1.0/1.0 1.0/1.0 type I N N N 3rd N KNOSP 214 7 0.80/1.0 1.0/1.0 type III S N N 3rd N KNOSP 415 9 1.0/1.0 1.0/1.0 type II N N N N N KNOSP 216 7 1.0/1.0 1.0/1.0 type I S S N 3rd N KNOSP 317 11 NLP/HM NLP/HM type I - - - 3rd N KNOSP 218 3 NLP 0.1/0.63 type I - - - 3rd 3rd KNOSP 419 8 HM/0.12 0.1/0.5 type I - - - N N KNOSP220 45 1.0/0.32 1.0/1.0 type II H I N N N KNOSP 421 11 CF/0.32 0.1/0.7 type III H I I N N KNOSP 122 5 1.0/0.1 1.0/0.63 type II H N N N N KNOSP 1

Table 4. Visual function evaluation and evolution taking into account the delay of surgery, initial deficit and local extension of tumor

+ VA – visual acuity, VF – visual field, CN – cranial nerves, OD – oculus dexter, OS – oculus sinister, N – normal, Q – quadranopsy, H – hemianopia, S – scotoma, I – improvement, NLP – no light perception, HM – hand movement, CF – counting fingers* Suprasellar extension – evaluated using the Hardy grading scale, # Lateral extension evaluated using the Knosp grading scale.

D.I. Rotariu et al.

60

difference between groups 2 and 3 (p=0.36, Student T-test). Postoperative VF analysis of patients who presented with VF defects (9 out of 14) showed: normalization of VF in 3 cases (33.33%), amelioration in 4 cases (44.44%), and no improvement in 2 cases (22.22%). Statistical analyses for our series showed a significant improvement of VF at 7 days postop after surgical treatment (p=0.0035, Student T-test). VF continued to improve also at 1 month postop evaluation. The VF presented significant amelioration compared with postop evaluation (p=0.049, Student T-test). Cranial nerve function presented amelioration in 8 cases of 10 with total resolution of symptomatology (p=0.005, Student T-test) but it was not influenced by the time of surgery (p=0.26, ANOVA). Records regarding the postoperative endocrine evaluation were available in 16 cases and showed pituitary deficiency with need for hormone replacement in 56% (9 out of 16). Four cases presented with pituitary deficiency and maintained the insufficiency after surgery and 5 had new postoperative deficiency, 7 patients had normal pituitary function. Diabetes insipidus (DI) was present in 50% of cases (11 patients). In eight it was transitory and in 3 it was permanent requiring substitution with desmopresine (Table 3). Other surgical complications were represented by meningitis in 1 case, late hydrocephalus needing ventricular derivation in 2 cases and 2 cases of perioperative deaths (1 case of mitral valve rupture and one case of fulminant pituitary insufficiency).

dIsCussIon

PA first described by Bailey in 1896 as a catastrophic haemorrhage of the pituitary adenoma (16) remains a se-vere and potential life threatening condi-tion, which in the absence of adequate treatment may lead to severe disabilities such as blindness, cranial nerve palsy, and pituitary dysfunction. Nowadays, PA is defined as a syndrome which re-sults from infarction, haemorrhage, or both of a pituitary tumour usually ad-enomas, and the consequence is the sud-den increase of the intrasellar volume with compression of the adjacent struc-tures resulting in altered level of con-sciousness, visual impairments, cranial nerve palsy and pituitary insufficiency (17, 18, 19). The incidence of PA var-ies from 0.8% to 22% according to dif-ferent studies (19, 20, 21). In our series the incidence of PA was 27.1% (22 out of 81). Different mechanisms have been proposed in order to explain the haemor-rhage and infarction including: ischemia into a rapidly growing adenoma, athero-sclerotic embolization, capillary fragility and direct compression of the infundibu-lum with alteration of blood flow (6, 7). The PA in our series was the first manifestation of a pituitary adenoma in 77.2% (17 cases) of cases, although symptoms of pituitary hormone abnormality may have been present before the acute event, but they remained unrecognized, similar results (81%) being reported by Semple et al. (6). All cases of PA emerged in patients harbouring macroadenomas, this being in accordance with previous works (22, 23, 24) who sustain that PA is the initial

Pituitary apoplexy

61

manifestation of macroadenoma. Most of PAs are spontaneous, also called primary although numerous precipitating factors were suggested. In 2001 Biousse et al. (23) grouped these factors in 4 categories: 1. Reduced blood flow - oscillating of arterial pressure, hypotension associated with surgery, infection, myocardial infarction (25, 26), changes in intracranial pressure associated with head trauma, modifications in CSF dynamics after spinal anesthesia, lumbar puncture, myelography and previous radiation therapy which affect blood vessel integrity (1, 9, 23). 2. Acute increase in the blood flow in the pituitary gland. 3. Stimulation tests of pituitary gland, after administration of GnRh, TRH, CRH it is believed that these hormones produce a sudden increase of the metabolic activity resulting in insufficient blood supply (23, 27, 28) the same mechanism being probably involved in oral contraception using oestrogens and in therapy with dopaminergic agonists (1, 21, 23). 4. Anticoagulated state. In our series precipitating factors were identi-fied in 41% cases and were represented by treatment with dopaminergic ago-nists, infection, myocardial infarction, anaemia (7 cases) with further investiga-tion needed in this direction. PA occurs in both hyper-functional and clinically non-functional tumours (9), but most often in clinically non-functioning macroadenomas (29). The clinics of PA may vary from mild symptoms to severe neurologic deficits or even death, usually the onset is sudden with headache being the first

symptom followed within hours by other deficits, in our series the headache was present in 72.7 % (16 cases), visual acuity was affected in 77% (17 cases) varying from decreased visual acuity to complete blindness, cranial nerves being involved in 45% (10 cases), 3rd nerve being the most affected, 45% (10 cases) of our series also presented visual field modifications; these modifications are due to sudden enlargement of intrasellar volume with upward or lateral extension and compression of the optic nerve and chiasma and cavernous sinus (2). The imagistic technique of choice is the MRI of the sellar region and it is used for diagnostic confirmation, pituitary mass with signs of haemorrhage or infarction, and appreciation of local extension of the tumour. We have analysed the suprasellar extension using the Hardy grading scale and observed a good correlation between upward extension and the degree of visual acuity decrease (r=0.501 n=22, p=0.018). The lateral extension was assessed using the Knosp grading scale (15) and the degree of ACI encasement, from these methods the score obtained using the Knosp scale is well correlated with the presence of cranial neuropathy (r=0.457, n=22, p=0.05), and the degree of ACI encasement is in direct correlation with the presence of cavernous sinus invasion (r=0.754, n=21, p=0.007). The results were obtained using the Pearson correlation method. The treatment of PA is conducted in regard of 2 points: surgical decompression and high dose corticoids in order to replace the pituitary insufficiency and careful management

D.I. Rotariu et al.

62

of water and electrolytes balance (1, 3, 9). Corticoid replacement is crucial in patients that are haemodynamically unstable (as a consequence of the acute secondary adrenal insufficiency), but it is also indicated in patients with altered level of consciousness, reduced visual acuity and severe altered visual field (29). The main indication for early surgical decompression (eventually after patient stabilisation) is represented by the presence of severe or acute visual deterioration. It is well known that the outcome of visual function (VF and VA) is improved if the surgery is performed within the first 7 days from onset (30). In our series 21 patients underwent surgical decompression and 1 was treated conservatorily due to an acute myocardial infarction; however, our patients had a long delay between the initial symptom and the surgical intervention which ranged from 3 days to 45 days with a mean of 11.7 days. As a result only 12 interventions were performed within the first 7 days, the recovery of visual function was statistically significantly higher in the group treated within the 1st week compared with the rest of interventions (p=0.032). We also remarked a difference between the interventions performed in the interval 7-14 days in comparison with interventions after 14 days. The recovery of visual acuity was also influenced by the aspect of the optic disc at fundoscopy, with poor results for patients who presented with total ON atrophy. The recovery was also influenced by the degree of affectation at admission, with poor results for patients presenting with a visual acuity lower than 0.1. The overall improvement of visual function in our

series was 78.5% (11 cases) for visual acuity, the visual field, however, had a time dependent evolution. At discharge 44.44% (4 cases) had improvement of VF, 22.22% (2 cases) had no modification and 33.33% (3 cases) had normalization of the VF. At 1 month the visual field continued to improve with normalization in 57.1% (8 cases) and improvement in 42.8% (6 cases) compared to the initial evaluation. As for cranial nerve involvement, we had an improvement of CN function after surgery (p=0.005), but the delay of surgical intervention had no effect on the recovery of cranial function (p=0.267), this fact also being noted by Maccagnan et al. (31), who described satisfactory results even after conservative treatment. Complete endocrine recovery was observed only in 2 cases (which presented with moderate pituitary deficiency), suggesting that surgery may also have a role in the endocrine recovery, but highly dependent on the degree of hypopituitarism after the initial attack (32). In our series all the patients harbouring secreting pituitary adenoma that suffered an apoplectic episode maintained high level of hormone secretion after apoplexy and after surgery, suggesting that surgery was effective only as an emergency procedure in order to save life and visual function, but it was not effective in treating the endocrine disease, although there are cases cited in the literature in which functional secreting adenomas showed a spontaneous normalization of hormone secretion after the apoplectic episode alone (33). The prevalence of DI at presentation, despite the suprasellar extension in pituitary apoplexy, is no

Pituitary apoplexy

63

more than 2-6% (17) of the cases in our series, but represented the main surgical complication in our series 7 cases of transitory DI and 3 cases of definitive DI. Another complication was represented by the postoperative pituitary insufficiency, 5 cases with need for long time hormonal substitution probably to the transcranian route used in the majority of cases In conclusion, PA remains a severe, potentially life threatening condition which needs a multidisciplinary approach. Altered level of consciousness, hypothalamic dysfunction and sudden visual deterioration are the indications for urgent surgical decompression. High-dose corticosteroid replacement should empirically be given to all patients presenting with haemodynamic instability, altered level of consciousness, decreased visual acuity and severe visual field defects. Early surgical decompression, within 7 days from onset, is correlated with visual function recovery and represents the standard approach. Cranial nerve palsy is correlated with the lateral extension of the tumor and tends to improve with time with or without surgery. Visual field defects usually improve after surgery and continue to improve in the late postop period. Pituitary dysfunction at presentation is usually irreversible and has a high occurrence after surgical decompression, with long time needed for hormone replacement. Given the long delay in our group between the onset of symptomatology and admission we believe that an educational and informational program is needed in order to reduce the time between onset and surgical intervention.

Conflict of interest The authors have no conflict of interest for this article.

References

1. Cardoso ER, Peterson EW. Pituitary apoplexy: A review. Neurosurgery 1984; 14(3): 363–373.2. Semple PL, Webb MK, de Villiers JC, Jacques C, Laws ER Jr: Pituitary apoplexy. Neurosurgery 2005; 56(1): 65–73.3. Bills DC, Meyer FB, Laws ER Jr, Davis DH, Ebersold MJ, Scheithauer BW, Ilstrup DM, Abboud CF. A retrospective analysis of pituitary apoplexy. Neurosurgery 1993; 33(4): 602–609.4. Mohr G, Hardy J. Hemorrhage, necrosis, and apoplexy in pituitary adenomas. Surg Neurol 1982; 18(3): 181–189.5. Onesti ST, Wisniewski T, Thomas, Post KD: Clinical versus subclinical pituitary apoplexy: Presentation, surgical management, and outcome in 21 patients. Neurosurgery 1990; 26 (6): 980–986.6. Semple P, Jane J, Lopes B, Laws E. Pituitary apoplexy: correlation between magnetic resonance imaging and histopathological results. J Neurosurg 2008; 108(5): 909–915.7. Rovit RL, Fein JM. Pituitary apoplexy: a review and reappraisal. J Neurosurg 1972; 37(3): 280-288. 8. Nawa R, AbdelMannan D, Selman W, Arafah B. Pituitary tumor apoplexy: a review. J Intens Care Med 2008; 23(2): 75–90.9. Randeva HS, Schoebel J, Byrne J, Esiri M, Adams CBT, Wass JAH: Classical pituitary apoplexy: clinical features, management and outcome. Clin Endocrinol (Oxf) 1999; 51(2): 181–188.10. De Villiers JC, Marcus G. Non-haemorrhagic infarction of pituitary tumors presenting as pituitary apoplexy. Adv Biosci 1988; 69(3): 461–464.11. Glick RP, Tiesi JA. Subacute pituitary apoplexy: clinical and magnetic resonance imaging characteristics. Neurosurgery 1990; 27(2): 214–218.12. Kyle CA, Laster RA, Burton EM, Sanford RA. Subacute pituitary apoplexy: MR and CT appearance. J Comput Assist Tomogr 1990; 14(1): 40–44.13. Semple PL, De Villiers JC, Bowen RM, Lopez MBS, Laws ER Jr. Pituitary apoplexy: do histological features influence the clinical presentation and outcome. J Neurosurg 2006;

D.I. Rotariu et al.

64

104(6): 931–937.14. R: Risk Factor Analysis on the Predictors of the Transsphenoidal Pituitary Surgery on Macroadenomas: A Multivariate Logistic Regression Analysis. Nepal Journal of Neuroscience 2006; 9 (1) 10-16,15. Knosp E, Steiner E, Kitz K, Matula C. Pituitary adenomas with invasion of the cavernous sinus space: a magnetic resonance imaging classification compared with surgical findings. Neurosurgery 1993; 33(4):610-617.16. Arafah BM, Harrington JF, Madhoun ZT, Selman WR. Improvement of pituitary function after surgical decompression for pituitary tumor apoplexy. J Clin Endocrinol Metab 1990; 71(2): 323-328.17. Bonneville F, Cattin F, Marsot-Dupuch K, Dormont D, Bonneville JF, Chiras J: T1 signal hyperintensity in the sellar region: spectrum of findings. Radiographics 2006; 26(1): 93–113.18. Riedl M, Clodi M, Kotzmann H, Hainfellner JA, Schima W, Reitner A, Czech T, Luger A. Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones: MR features. Eur J Radiol 2000; 36(1):1-4.19. Dubuisson AS, Beckers A, Stevenaert A. Classical pituitary tumour apoplexy: clinical features, management and outcomes in a series of 24 patients. Clinical Neurology and Neurosurgery 2007; 109(1): 63–70.20. Brisman BH, Katz G, Post KD: Symptoms of pituitary apoplexy rapidly reversed with bromocriptine. J Neurosurg 1996; 85(6): 1153–1155.21. Liu ZH, Chang CN, Pai PC, Wei KC, Jung SM, Chen NY & Chuang CC. Clinical features and surgical outcome of clinical and subclinical pituitary apoplexy. Journal of Clinical Neuroscience 2010; 17(6): 694–699.22. Jeffcoate WJ & Birch CR. Apoplexy in small pituitary tumours. J Neurol Neurosurg Psychiatry 1986; 49(9): 1077-1078.23. Biousse V, Newman NJ, Oyesiku NM. Precipitating factors in pituitary apoplexy. J Neurol Neurosurg Psychiatry. 2001; 71(4): 542–545.

24. Milazzo S, Toussaint P, Proust F, Touzet G, Malthieu D. Ophthalmologic aspects of pituitary apoplexy. Eur J Ophthalmol. 1996; 6(1): 69–73.25. Glass LC. Images in clinical medicine: pituitary apoplexy. N Engl J Med. 2003; 349 (21): 2034. 26. Nagarajan DV, Bird D, Papouchado M. Images in cardiology: pituitary apoplexy following anticoagulation for acute coronary syndrome. Heart. 2003; 89(1): 10.27. Matsuura I, Saeki N, Kubota M, Murai H, Yamaura A: Infarction followed by hemorrhage in pituitary adenoma due to endocrine stimulation test. Endocr J 2001; 48(4): 493–498.28. Rotman-Pikielny P, Patronas N, Papanicolaou DA: Pituitary apoplexy induced by corticotrophin-releasing hormone in a patient with Cushing’s disease. Clin Endocrinol (Oxf) 2003; 58(5): 545–549.29. Senthil Rajasekaran, Mark Vanderpump, Stephanie Baldeweg, Will Drake, Narendra Reddy, Marian Lanyon, Andrew Markey, Gordon Plant, Michael Powell, Saurabh Sinha and John Wass: UK Guidelines for the Management of Pituitary apoplexy. Clinical Endocrinology 2011; 74(1): 9–20.30. da Motta LA, de Mello PA, de Lacerda CM, Neto AP, da Motta LD, Filho MF: Pituitary apoplexy: Clinical course, endocrine evaluations and treatment analysis. J Neurosurg Sci 1999; 43(1): 25–36.31. Maccagnan P, Macedo CL, Kayath MJ, Nogueira RG, Abucham J. Conservative management of pituitary apoplexy: A prospective study. J Clin Endocrinol Metab 1995; 80(7): 2190–2197.32. Petra Nadja Elsa¨sser Imboden, MD, Nicolas De Tribolet, MD, Alexander Lobrinus, MD, Rolf C. Gaillard, MD, Luc Portmann, MD, Francois Pralong, MD, and Fulgencio Gomez MD: Apoplexy in Pituitary Macroadenoma. Medicine 2005; 84(3): 188-196.33. Chentli F, Terki B, Djerradi L, Belhimer F, Azzoug S: Cure of Acromegaly and Diabetes Mellitus After Pituitary Apoplexy. Acta Endo (Buc) 2012 8(1): 113-118.