Several medications used in the management of pituitary tumours had been implicated as precipitating factor for pituitary apoplexy. Bromocriptine, a dopamine receptor agonist, used in the treatment of prolactin-producing tumours is commonly implicated. Pituitary apoplexy might occur a few weeks after discontinuation of bromocriptine which might be due to acute enlargement of the pituitary adenoma (Biousse et al. 2001). There were other studies reporting pituitary apoplexy in prolactin-secreting pituitary macroadenomas while on bromocriptine therapy (Pinto et al. 1998; Imboden et al. 2005).

Patients with acromegaly had also developed pituitary apoplexy during bromocriptine therapy. Necrosis of adenoma due to bromocriptine might be responsible for apoplexy (Wakai et al. 1981).

Cabergoline, the newer dopamine receptor agonist which is now widely used because of lesser side effects, had also been shown to be a precipitating factor for pituitary apoplexy in several studies (Knoepfelmacher et al. 2004; Dubuisson et al. 2007; Balarini Lima et al. 2008).

Clomiphene has also been associated with pituitary apoplexy. Pituitary apoplexy occurred in a patient with GH-secreting pituitary macroadenoma after clomiphene therapy. Clomiphene might lead to infarction of tumour by increasing the blood GnRH concentration thereby indirectly leading to vasospasm or rapid tumour expansion with the resultant ischaemic necrosis (Walker et al. 1996).

Octreotide, a somatostatin analogue, is another drug shown to be associated with pituitary apoplexy. Patient with acromegaly might develop pituitary apoplexy after stopping subcutaneous octreotide (Sibal et al. 2004).

Various surgical procedures have been implicated in pituitary apoplexy. Semple et al. (2007) reported four patients with known pituitary adenomas who developed pituitary apoplexy. Two macroadenomas on conservative management developed pituitary apoplexy after hip replacement surgery and orchidectomy.

Pituitary apoplexy has been reported in patients who underwent partial resection for large pituitary tumours. Goel et al. (1995) described two cases of pituitary apoplexy in residual tumours after partial resection of giant pituitary tumours. Surgery might compromise blood supply to remaining tumour resulting in apoplexy (Ahmad et al. 2005).

Pituitary stimulation tests have been implicated as a cause in many cases of pituitary apoplexy. Pituitary apoplexy had been reported in patient with pituitary macroadenoma with suprasellar extension following TRH testing (Szabolcs et al. 1997). Similar report was also available in case of acromegaly following TRH stimulation test (Wang et al. 2007).

Several mechanisms have been postulated for apoplexy after pituitary stimulation test. TRH-induced vasospasm may precipitate pituitary gland infarction (Bernstein et al. 1984). Pressure effect of catecholamines released after TRH injection may precipitate pituitary tumour infarction (Dokmetas et al. 1999). Direct effect of TRH on tumour cells along with increased blood flow and volume thereby may lead to abrupt tumour expansion and pituitary apoplexy (Okuda et al. 1994; Masago et al. 1995).

For the first time in 1984, pituitary apoplexy in a FSH-secreting adenoma, which developed infarction after GnRH, was described (Korsic et al. 1984). Following that there were several reports of pituitary apoplexy in patients with macroadenoma after GnRH (Arafah et al. 1989; Masson et al. 1993; Hiroi et al. 2001). Acute GnRH stimulation of gonadotropic cells might increase the metabolic activity of the tumour, resulting in excessive gonadotropin production to such an extent that a vascular accident could occur (Korsic et al. 1984). GnRH might also have a direct action on tumour vasculature (Masson et al. 1993; White and Masson 1994).

Several cases of pituitary apoplexy after TRH and GnRH stimulation test had been reported (Masago et al. 1995; Dokmetas et al. 1999; Lee et al. 2000; Kilicli et al. 2010). Triple stimulation tests using GnRH, TRH and insulin might also lead to pituitary apoplexy (Okuda et al. 1994; Masago et al. 1995; Lee et al. 2000; Matsuura et al. 2001; Yoshino et al. 2007).

Pituitary apoplexy may also develop with other stimulation tests. Pituitary apoplexy had developed in Cushing’s disease following CRH administration (Rotman-Pikielny et al. 2003) and also after metyrapone test (Sibal et al. 2004).

There were reports of apoplexy in patients with pituitary adenoma following radiological procedures. Apoplexy had been reported after cerebral angiography in a case of GH-secreting pituitary macroadenoma (Louwerens et al. 1996). Pituitary apoplexy might occur following air encephalography (AEG) performed to delineate the extent of tumour (Sahdev et al. 1981). Pituitary apoplexy had also occurred following administration of Gd-DTPA in acromegaly (Wichers et al. 1997).

Patients with acromegaly might develop pituitary apoplexy after external irradiation (Sachdev et al. 1981; Wakai et al. 1981). Also reported pituitary apoplexy had been reported within 12 h of Gamma Knife surgery (Semple et al. 2007). Patient with known pituitary tumour might develop pituitary apoplexy with no predisposing factor (Semple et al. 2007).