Pituitary Apoplexy Associated with Endocrine Stimulation Test: Endocrine Stimulation Test, Treatment, and Outcome

Yamamoto, Takahiro; Yano, Shigetoshi; Kuroda, Jun-ichiro; Hasegawa, Yu; Hide, Takuichiro; Kuratsu, Jun-ichi

doi:https://doi.org/10.1155/2012/826901

Case Reports in Endocrinology

On this page

Abstract Introduction Case Presentation Discussion References Copyright Related Articles

Case Report | Open Access

Volume 2012 | Article ID 826901 | https://doi.org/10.1155/2012/826901

Pituitary Apoplexy Associated with Endocrine Stimulation Test: Endocrine Stimulation Test, Treatment, and Outcome

Takahiro Yamamoto,¹Shigetoshi Yano,¹Jun-ichiro Kuroda,¹Yu Hasegawa,¹Takuichiro Hide,¹and Jun-ichi Kuratsu¹

Academic Editor: W. V. Moore, S. Simsek, C. Capella

Received11 Mar 2012

Accepted14 May 2012

Published15 Aug 2012

Abstract

Pituitary apoplexy is a rare clinical syndrome attributable to hemorrhage or hemorrhagic infarction of pituitary tumors or pituitary glands. The features of pituitary apoplexy associated with the endocrine stimulation test remain to be elucidated and the importance of surgical treatment has not been discussed enough. We report two rare patients who were treated successfully by endoscopic endonasal transsphenoidal surgery within several hours after onset of pituitary apoplexy associated with the endocrine stimulation test. Their postoperative course was uneventful. We reviewed earlier reports on this clinical entity, document its features especially as related to the endocrine stimulation test, discuss the significance of immediate surgical treatment, and present our treatment outcomes. Performing only conservative treatment is not recommended. We suggest that the necessity of endocrine stimulation test should be assessed on a case-by-case basis and in patients subjected to the test, and neurosurgical support should be sought.

1. Introduction

Pituitary apoplexy is a life-threatening clinical syndrome thought to be attributable to hemorrhage or hemorrhagic infarction of pituitary tumors or pituitary glands [1]. Suggested precipitating factors are hypertension, anticoagulation, and bromocriptine therapy, and pregnancy [2–27]. There are few reports on the occurrence of pituitary apoplexy as a complication of the endocrine stimulation test, and its features remain to be elucidated. We report two rare patients with pituitary apoplexy associated with the endocrine stimulation test who were treated successfully by surgery and present a review of the literature. We also discussed about the necessity of neurosurgical support.

2. Case Presentation

2.1. Case 1

A 56-year-old woman with a one-year history of visual disturbance was admitted to our hospital for the evaluation of a suprasellar tumor. Physical examination at admission revealed visual disturbance (temporal hemianopia on the left side) but no other neurological disorders or endocrinological symptoms. Her baseline levels of pituitary hormones were normal. Computed tomography (CT) and magnetic resonance imaging (MRI) studies demonstrated a pituitary adenoma with suprasellar extension and superior displacement of the optic chiasm. To evaluate her hormonal responses we performed combined endocrine stimulation tests with growth-hormone-releasing hormone (GRH, 100 μg), thyrotropin-releasing hormone (TRH, 250 μg), luteinizing hormone-releasing hormone (LH-RH, 100 μg), and corticotrophin-releasing hormone (CRH, 100 μg). Fifteen minutes after the intravenous bolus injection she complained of severe headache, and this was followed by vomiting, progressive visual disturbance, and left oculomotor paralysis. She was alert but her symptoms gradually worsened. Emergency CT and MRI revealed intratumoral hemorrhage (Figures 1(a)–1(d)). Four hours after onset, her left visual acuity was reduced to total blindness; there was temporal hemianopia in the right visual field. At emergency endoscopic endonasal transsphenoidal surgery was (ETSS) performed 5 hr after onset. Partially, tumor was solid and reddish-brown, different from the typical feature of pituitary adenoma. The tumor was totally removed. Pathological examination revealed hemorrhagic and necrotic area in nonnecrotic papillary-patterned tumor tissue (Figure 1(e)). Postoperatively, her headache, nausea and left oculomotor paralysis resolved, and her vision returned to the preonset level. Because of her diabetes insipidus (DI) she received transient desmopressin replacement therapy. She was able to resume her normal life.

(a)

(b)

(c)

(d)

(e)

Figure 1

Case 1. CT scan performed 1 hr after onset demonstrates intratumoral hemorrhage (a), T1-weighted MRI showing a pituitary tumor extending into the suprasellar cistern (b), after onset gadolinium enhanced coronal T1-weighted MRI showing no enhancement of the pituitary tumor (c), T2-weighted MRI showing a pituitary tumor with a low-signal-intensity rim. This finding was suggestive of pituitary apoplexy (d), Specimen stained with hematoxylin and eosin. Hemorrhage and necrosis on the right side of the picture and area of nonnecrotic papillary-patterned tumor tissue on the left (e).

2.2. Case 2

A 73-year-old man with an 8-month history of visual disturbance was referred to our hospital. Five years earlier, when he was diagnosed with suprasellar tumor, he was asymptomatic and without visual disturbance. In the intervening five years, his tumor gradually enlarged and became symptomatic. At admission to our hospital, visual field examination revealed temporal hemianopia on the left side. He had no other neurological disorders or endocrinological symptoms. His baseline pituitary hormone levels were normal. CT and MRI demonstrated a pituitary adenoma with suprasellar extension and superior displacement of the optic chiasm. For preoperative endocrine evaluation we performed combined endocrine stimulation tests with growth hormone releasing peptide-2 (GHRP2, 100 μg), TRH (250 μg), LH-RH (100 μg), and CRH (100 μg). Twenty minutes after the intravenous bolus injection he complained of progressive visual disturbance. He was alert and experienced neither headache nor nausea. Emergency CT and MRI performed one hr after onset showed no evidence of intratumoral hemorrhage (Figures 2(a)–2(c)), two hr after onset his left visual acuity was reduced to total blindness. There was no visual disturbance on the right side. He underwent ETSS 5 hr after onset, and the tumor was totally removed. Same as Case 1, tumor was partially solid and reddish-brown. Pathological examination revealed papillary-patterned adenoma with diffuse hemorrhage and necrosis (Figure 2(d)). His postoperative course was uneventful. One month after the operation his visual disturbance resolved completely, and he required no hormone replacement therapy.

(a)

(b)

(c)

(d)

Figure 2

Case 2. CT scan performed 1 hour after onset demonstrates no evidence of intratumoral hemorrhage or acute enlargement of the tumor size (a), T1-weighted MRI performed after onset shows a pituitary tumor extending into the suprasellar cistern. There was no evidence of intratumoral hemorrhage or acute infarction (b), after onset gadolinium-enhanced T1-weighted MRI showing uniform enhancement of the pituitary tumor (c), and pathological examination revealed papillary-patterned adenoma with diffuse hemorrhage and necrosis (d).

3. Discussion

Pituitary apoplexy is a rare clinical syndrome thought to be attributable to hemorrhage or hemorrhagic infarction of pituitary tumors or pituitary glands. It is characterized by the sudden onset of headache, vomiting, visual impairment, and decreased consciousness. Reported precipitating factors of pituitary apoplexy are hypertension, anticoagulation and bromocriptine therapy, pregnancy, and angiography [1, 22]. Although pituitary apoplexy associated with the endocrine stimulation test has been reported (Table 1), its features remain to be elucidated [2–27]. Of the 32 previously-reported patients and our two patients with pituitary adenomas who experienced pituitary apoplexy, 16 (47%) had nonfunctioning, 8 (23.5%) GH-secreting, 5 (14.7%) prolactin (PRL)-secreting, 3 (8.8%) follicle-stimulating hormone (FSH)-secreting, and 2 (5.9%) had adrenocorticotropic hormone (ACTH)-secreting adenomas. This proportion is similar to the frequency among the types of pituitary adenomas [28]. This suggests that there is no strong correlation between the types of pituitary adenoma and the elicitation of pituitary apoplexy by the endocrine stimulation test. On the other hand, there appears to be a relationship between the size of pituitary adenomas and pituitary apoplexy associated with the endocrine stimulation test. Our review of the literature showed that 93% of previouslyn reported patients manifested extrasellar extension of their pituitary tumors. TRH (26 cases, 76.4%) and LH-RH (23 cases, 67.6%) were the hormonal stimulants most commonly associated with the elicitation of pituitary apoplexy. Although the precise mechanisms of pituitary apoplexy associated with TRH- and LH-RH stimulation remain unclear, it has been suggested that TRH elevates the serum level of norepinephrine, and that vasospasm or pressor effects may be precipitating factors [3, 15, 29]. Others proposed that TRH directly activates the tumor cells, or that LH-RH stimulation increases metabolic activity leading to vascular accidents [6, 12, 15, 18, 29]. Interestingly, the number of hormonal stimulants used in the endocrine stimulation test has no bearing on the elicitation of pituitary apoplexy; the Spearman correlation was with a value of 0.6 (Table 1(a)). Excluding the two patients reported here, the incidence of pituitary apoplexy among patients subjected to the endocrine stimulation test with four stimulants was 0 in our department. Because this test is convenient and the incidence of test-elicited pituitary apoplexy is low, it is used widely to investigate the reserve function of the pituitary in patients with pituitary adenoma. Nonetheless, based on earlier reports and our experience with the two patients reported here, we think that the necessity for performing the endocrine stimulation test must be evaluated on a case-by-case basis.

Among the 34 patients, detailed treatments and outcomes were available in 23 (Table 1(b)); 20 patients underwent surgery, and the other 3 were treated conservatively [3, 4, 7, 8, 11, 13–15, 17–23, 26, 27, 29]. Of the latter, all experienced symptom exacerbation after suffering pituitary apoplexy [7, 8, 14, 21, 26]. Among the 20 surgically treated patients, in 14 the symptoms worsened after the occurrence of pituitary apoplexy while in the other six they were unchanged or improved [3, 4, 11, 13, 15, 17–20, 22, 23, 27, 29]. In three patients who underwent tumor removal on the day of onset of pituitary apoplexy, the symptoms were worse after than before onset while in another four they were improved or unchanged [3, 11, 15, 18, 29]. In our cases, the patients underwent surgery within 5 hr of apoplexy onset, the symptoms attributable to pituitary apoplexy were improved. Because pituitary apoplexy associated with the above-cited precipitating factors is rare, controversy continues to surround the standard treatment [1]. In some instances the symptoms associated with precipitating factors improved when surgery was performed within 7-8 days of apoplexy onset [1, 30].

Our review of the literature suggests that patients with pituitary apoplexy elicited by the endocrine stimulation test should be operated within several hours after its onset, that is, sooner than patients with pituitary apoplexy associated with the other precipitating factors. Performing only conservative treatment is not recommended. We recommend that the necessity for endocrine stimulation tests should be considered carefully and that they be performed with neurosurgical support.

References

S. Rajasekaran, M. Vanderpump, S. Baldeweg et al., “UK guidelines for the management of pituitary apoplexy,” Clinical Endocrinology, vol. 74, no. 1, pp. 9–20, 2011.
View at: Publisher Site | Google Scholar
B. M. Arafah, J. F. Harrington, Z. T. Madhoun, and W. R. Selman, “Improvement of pituitary function after surgical decompression for pituitary tumor apoplexy,” Journal of Clinical Endocrinology and Metabolism, vol. 71, no. 2, pp. 323–328, 1990.
View at: Google Scholar
M. Bernstein, R. A. Hegele, F. Gentili et al., “Pituitary apoplexy associated with a triple bolus test. Case report,” Journal of Neurosurgery, vol. 61, no. 3, pp. 586–590, 1984.
View at: Google Scholar
A. J. Chapman, G. Williams, A. D. Hockley, and D. R. London, “Pituitary apoplexy after combined test of anterior pituitary function,” British Medical Journal, vol. 291, no. 6487, p. 26, 1985.
View at: Google Scholar
A. Cimino, R. Corsini, E. Radaeli, A. Bollati, and G. Giustina, “Transient amaurosis in patient with pituitary macroadenoma after intravenous gonadotropin and thyrotropin releasing hormones,” The Lancet, vol. 2, no. 8237, p. 95, 1981.
View at: Google Scholar
H. S. Dökmetaş, A. Selçuklu, R. Çolak, K. Ünlühizarci, F. Bayram, and F. Keleştimur, “Pituitary apoplexy probably due to TRH and GnRH stimulation tests in a patient with acromegaly,” Journal of Endocrinological Investigation, vol. 22, no. 9, pp. 698–700, 1999.
View at: Google Scholar
P. L. Drury, P. E. Belchetz, W. I. McDonald, D. G. Thomas, and G. M. Besser, “Transient amaurosis and headache after thyrotropin releasing hormone,” The Lancet, vol. 1, no. 8265, pp. 218–219, 1982.
View at: Google Scholar
P. J. Dunn, R. A. Donald, and E. A. Espiner, “Regression of acromegaly following pituitary apoplexy,” Australian and New Zealand Journal of Medicine, vol. 5, no. 4, pp. 369–372, 1975.
View at: Google Scholar
R. Harvey, M. Michelagnoli, P. McHenry, D. G. Currie, and P. D. Bewsher, “Pituitary apoplexy,” British Medical Journal, vol. 298, no. 6668, p. 258, 1989.
View at: Google Scholar
R. M. Jordan, D. M. Cook, J. W. Kendall, and C. W. Kerber, “Nelson's syndrome and spontaneous pituitary tumor infarction,” Archives of Internal Medicine, vol. 139, no. 3, pp. 340–342, 1979.
View at: Publisher Site | Google Scholar
F. Kiliçli, H. S. Dökmetaş, and M. Gürelik, “Development of pituitary apoplexy during TRH/GnRH test in a patient with pituitary macroadenoma,” Singapore Medical Journal, vol. 51, no. 11, pp. e179–e181, 2010.
View at: Google Scholar
M. Korsic, “Pituitary apoplexy following the administration of gonadotrophin releasing hormone,” Clinical Endocrinology, vol. 41, no. 5, pp. 696–697, 1994.
View at: Publisher Site | Google Scholar
D. H. Lee, M. Y. Chung, D. J. Chung et al., “Apoplexy of pituitary macroadenoma after combined test of anterior pituitary function,” Endocrine Journal, vol. 47, no. 3, pp. 329–333, 2000.
View at: Google Scholar
E. G. Lever, J. Butler, and P. Moore, “Infarction of a growth hormone-secreting macroadenoma during a TRH test,” Acta Endocrinologica, vol. 112, no. 2, pp. 172–179, 1986.
View at: Google Scholar
A. Masago, Y. Ueda, H. Kanai et al., “Pituitary apoplexy after pituitary function test: a report of two cases and review of the literature,” Surgical Neurology, vol. 43, no. 2, pp. 158–165, 1995.
View at: Publisher Site | Google Scholar
E. A. Masson, S. L. Atkin, M. Diver, and M. C. White, “Pituitary apoplexy and sudden blindness following the administration of gonadotrophin releasing hormone,” Clinical Endocrinology, vol. 38, no. 1, pp. 109–110, 1993.
View at: Google Scholar
I. Matsuura, N. Saeki, M. Kubota, H. Murai, and A. Yamaura, “Infarction followed by hemorrhage in pituitary adenoma due to endocrine stimulation test,” Endocrine Journal, vol. 48, no. 4, pp. 493–498, 2001.
View at: Google Scholar
O. Okuda, H. Umezawa, and M. Miyaoka, “Pituitary apoplexy caused by endocrine stimulation tests: a case report,” Surgical Neurology, vol. 42, no. 1, pp. 19–22, 1994.
View at: Publisher Site | Google Scholar
F. Otsuka, J. Kageyama, T. Ogura, and H. Makino, “Pituitary apoplexy induced by a combined anterior pituitary test: case report and literature review,” Endocrine Journal, vol. 45, no. 3, pp. 393–398, 1998.
View at: Google Scholar
M. Riedl, M. Clodi, H. Kotzmann et al., “Apoplexy of a pituitary macroadenoma with reversible third, fourth and sixth cranial nerve palsies following administration of hypothalamic releasing hormones: MR features,” European Journal of Radiology, vol. 36, no. 1, pp. 1–4, 2000.
View at: Publisher Site | Google Scholar
P. Rotman-Pikielny, N. Patronas, and D. A. Papanicolaou, “Pituitary apoplexy induced by corticotrophin-releasing hormone in a patient with Cushing's disease,” Clinical Endocrinology, vol. 58, no. 5, pp. 545–549, 2003.
View at: Publisher Site | Google Scholar
N. Sanno, Y. Ishii, M. Sugiyama, R. Takagi, Y. Node, and A. Teramoto, “Subarachnoid haemorrhage and vasospasm due to pituitary apoplexy after pituitary function tests,” Acta Neurochirurgica, vol. 141, no. 9, pp. 1009–1010, 1999.
View at: Publisher Site | Google Scholar
K. Shirataki, K. Chihara, Y. Shibata, N. Tamaki, S. Matsumoto, and T. Fujita, “Pituitary apoplexy manifested during a bromocriptine test in a patient with a growth hormone- and prolactin-producing pituitary adenoma,” Neurosurgery, vol. 23, no. 3, pp. 395–398, 1988.
View at: Google Scholar
V. E. Silverman, A. E. Boyd, J. A. McCrary III, and P. O. Kohler, “Pituitary apoplexy following chlorpromazine stimulation,” Archives of Internal Medicine, vol. 138, no. 11, pp. 1738–1739, 1978.
View at: Publisher Site | Google Scholar
I. Szabolcs, N. Késmárki, K. Bor et al., “Apoplexy of a pituitary macroadenoma as a severe complication of preoperative thyrotropin-releasing hormone (TRH) testing,” Experimental and Clinical Endocrinology and Diabetes, vol. 105, no. 4, pp. 234–236, 1997.
View at: Google Scholar
M. Vassallo, Z. Rana, and S. Allen, “Pituitary apoplexy after stimulation tests,” Postgraduate Medical Journal, vol. 70, no. 824, pp. 444–445, 1994.
View at: Google Scholar
H. F. Wang, C. C. Huang, Y. F. Chen, D. M. T. Ho, and H. D. Lin, “Pituitary apoplexy after thyrotropin-releasing hormone stimulation test in a patient with pituitay macroadenoma,” Journal of the Chinese Medical Association, vol. 70, no. 9, pp. 392–395, 2007.
View at: Publisher Site | Google Scholar
G. Mohr and J. Hardy, “Hemorrhage, necrosis, and apoplexy in pituitary adenomas,” Surgical Neurology, vol. 18, no. 3, pp. 181–189, 1982.
View at: Google Scholar
A. Yoshino, Y. Katayama, T. Watanabe et al., “Apoplexy accompanying pituitary adenoma as a complication of preoperative anterior pituitary function tests,” Acta Neurochirurgica, vol. 149, no. 6, pp. 557–565, 2007.
View at: Publisher Site | Google Scholar
Y. Hasegawa, S. Yano, T. Sakurama et al., “Endoscopic surgical treatment for pituitary apoplexy in three elderly patients over the age of 80,” Acta Neurochirurgica Supplementum, vol. 111, part 6, pp. 429–433, 2011.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2012 Takahiro Yamamoto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

3133

Downloads

1770

Citations