Pituitary apoplexy: considerations on a single center experience and review of the literature

Giammattei, Lorenzo; Mantovani, Giovanna; Carrabba, Giorgio; Ferrero, Stefano; Cristofori, Andrea Di; Verrua, Elisa; Guastella, Claudio; Rampini, Paolo; Minichiello, M.; Locatelli, Marco

doi:10.1007/s40618-015-0424-2

Cited by 17 publications

(20 citation statements)

References 58 publications

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“…30 All tumors in our case series were macroadenomas, and as occurs in the published literature, 3,4,18,23,26,27 our case series comprised mostly nonfunctional adenomas (70%), with only 15% of adenomas demonstrating hormone hypersecretion (3 prolactinomas, 1 somatotrophinoma). The fact that apoplexy is more often associated with larger tumors, which is well reported in the literature, 6,7,18,20,23,30,33,36 is purportedly due to the increased tumor size outstripping blood supply and resulting in ischemia and/or hemorrhage. It has been suggested that features intrinsic to the biology of apoplectic adenomas, such as high metabolic demand with concomitant limited vascular supply, hypoglycemia, and limited nutrient supply, may predispose to ischemia and hemorrhage.…”

Section: Discussionmentioning

confidence: 91%

Surgical intervention for pituitary apoplexy: an analysis of functional outcomes

Rutkowski¹,

Kunwar²,

Blevins³

et al. 2018

Journal of Neurosurgery

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OBJECTIVE Pituitary apoplexy is a clinical syndrome consisting of neurological and endocrine abnormalities secondary to hemorrhage or ischemia of an underlying pituitary adenoma. The authors investigated whether there was a significant difference in neurological, endocrine, and nonneuroendocrine outcomes for patients with pituitary apoplexy, based on the time between symptom onset and surgical intervention. METHODS The authors retrospectively analyzed the medical records of 32 patients who had presented to their institution with acute pituitary apoplexy and subsequently undergone endonasal transsphenoidal resection in the period from 2003 to 2014. All patients had undergone preoperative MRI demonstrating evidence of apoplexy in the form of intratumoral hemorrhage, ischemia, and necrosis. Neurological deficits, partial or complete endocrinopathy, and nonneuroendocrine abnormalities were analyzed both pre- and postoperatively. RESULTS Preoperatively, neurological deficits including visual loss and cranial nerve palsies were found in 31 (97%) of the 32 patients, endocrinopathy in the form of partial or panhypopituitarism was seen in 28 patients (88%), and nonneuroendocrine signs and symptoms were seen in 32 patients (100%). Thirteen patients (41%) underwent surgery within 72 hours of symptom onset ("early"), whereas 19 patients (59%) underwent surgery more than 72 hours from symptom onset ("delayed"). Early versus delayed resection did not appear to significantly improve visual deficits, total visual loss, resolution of oculomotor palsy, recovery from hypopituitarism, or nonneuroendocrine signs and symptoms such as headache and encephalopathy. Overall, visual improvement was seen in 77% of patients, complete restoration of normal vision in 38% of patients, and resolution of preoperative oculomotor palsies in 81% of patients. Only 6 (21%) of 28 patients showed evidence of partial hormone recovery following preoperative hypopituitarism. An absence of benefit for early surgery held true even when considering time to surgery from symptom onset as a continuous variable. CONCLUSIONS Neurological deficits such as visual loss and cranial neuropathies show moderate improvement following surgical decompression, as does preoperative hypopituitarism. The timing of surgical intervention relative to the onset of symptoms does not appear to significantly affect the resolution of neurological or endocrinological deficits.

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Section: Discussionmentioning

confidence: 91%

Surgical intervention for pituitary apoplexy: an analysis of functional outcomes

Rutkowski¹,

Kunwar²,

Blevins³

et al. 2018

Journal of Neurosurgery

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“…The only concern with ASA as a potential therapeutic agent in pituitary adenomas is the risk of pituitary apoplexy. There are reports suggesting anticoagulant therapy as relative contraindication in patients with known macroadenoma [ 28 ]. However, patients with macroadenoma who had pituitary apoplexy received aggressive anticoagulative and antiplatelet therapy (ASA combined with clopidogrel and full-dose enoxaparin), therefore, it is unclear if ASA administration as a single therapy would increase the risk of apoplexy [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Survivin as a potential therapeutic target of acetylsalicylic acid in pituitary adenomas

et al. 2018

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Acetylsalicylic acid (ASA) is known as a cancer preventing agent, but there is no data available regarding the effect of ASA on pituitary cells.We investigated 66 nonfunctioning (NFPA) and growth hormone (GH)-producing adenomas and 15 normal pituitary samples. Functional assays (cell viability, proliferation, flow cytometry cell cycle analysis, caspase-3 activation and DNA degradation) were applied to explore the effect of ASA, YM155 (survivin inhibitor), survivin-targeting siRNA and TNF-related apoptosis-inducing ligand (TRAIL) in RC-4B/C and GH3 cells. Pituitary adenoma xenografts were generated in immunocompromised mice.We found that survivin was overexpressed and TRAIL was downregulated in NFPAs compared to normal pituitary tissue. ASA decreased proliferation but did not induce apoptosis in pituitary cells. Additionally, ASA treatment decreased cells in S phase and increased cells in G2/M phase of the cell cycle. Inhibition of survivin using an inhibitor or siRNA-mediated silencing reversed the ASA-induced growth inhibition partially. In addition, we also found survivin-independent effects of ASA on the cell cycle that were mediated through inhibition of cyclin A, cyclin dependent kinase 2 (CDK2) and phospho-CDK2. We also aimed to test the effect of acetylsalicylic acid in an animal model using RC-4 B/C cells, but in contrast to GH3 cells, RC-4 B/C cells failed to adhere and grow a xenograft.We concluded that ASA inhibited the growth of pituitary adenoma cells. Survivin inhibition is a key mechanism explaining its antineoplastic effects. Our results suggest that inhibition of survivin with small molecules or ASA could serve as potential therapeutic agents in NFPA.

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“…Pituitary apoplexy typically occurs in pituitary macroadenomas; the majority of the cases are spontaneous, and numerous precipitating factors have been reported (9,11,18,19). The mechanism underlying the development of pituitary apoplexy has been proposed to be reduced blood flow in the pituitary gland, acute increase in blood flow in the gland, stimulation of the gland, and the anticoagulant state (7,19) The maximum diameter of pituitary adenomas with intratumoral hemorrhage was significantly smaller in the patients in group C than in groups A and B. In contrast, the proportion of hemorrhage within the adenomas was significantly higher in the patients in group C, compared with both groups A and B.…”

Section: Discussionmentioning

confidence: 99%

Contribution of sellar dura integrity to symptom manifestation in pituitary adenomas with intratumoral hemorrhage

et al. 2017

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Pituitary apoplexy: considerations on a single center experience and review of the literature

Cited by 17 publications

References 58 publications

Surgical intervention for pituitary apoplexy: an analysis of functional outcomes

Surgical intervention for pituitary apoplexy: an analysis of functional outcomes

Survivin as a potential therapeutic target of acetylsalicylic acid in pituitary adenomas

Contribution of sellar dura integrity to symptom manifestation in pituitary adenomas with intratumoral hemorrhage

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