male macroprolactinomas ( mprl ) are usually revealed by headaches , visual troubles and gonadal insufficiency .
suppurative meningitis ( sm ) , a life - threatening condition , is scarcely observed in subjects with macro tumors secreting prolactin ( prl ) and in other pituitary tumors ( pt ) .
however , in some very rare cases it can be a primary presentation or appear after radiotherapy or medical treatment used for tumors destroying the sellar floor and/or the skull base .
this destruction leads to cerebral spinal fluid ( csf ) leak , which can act as an entry portal for organisms predisposing to meningitis .
our aim was to analyze sm frequency among male mprl deemed to be very invasive tumors , to report our cases and analyze the circumstances under which the dangerous neurological complication appeared .
in this retrospective study , we analyzed 82 subjects with mprl to look for symptoms , clinical signs and biological proof of sm .
, we took into account medical history , clinical examination , routine exploration , csf analysis and hormonal assessment .
that one was based on prl , growth hormone ( gh ) , insulin growth hormone ( igf1 ) , cortisol , adrenocorticotropic hormone , testosterone , follicle stimulating hormone , luteinizing hormone , thyroid stimulating hormone and free thyroxin .
radiological assessment was based on cerebral computed tomography scan and/or magnetic resonance imaging ( mri ) .
three were first hospitalized in the department of infectious diseases for typical symptoms and signs of sm ; that one was proved by csf biochemical analyses .
the fourth one was hospitalized in our department for the fourth episode of sm which was proved by csf analysis after lumbar puncture .
cerebral mri showed a pt invading cavernous sinuses , the sphenoid sinus and the brain [ figure 1 ] . hormonal assessment [ table 1 ] demonstrated high prl with gonadotroph deficit .
then , the pt was treated with dopamine agonists that were successful on prl ( 25 ng / ml ) and on tumor size [ figure 1 ] . after a follow - up of 7 years ,
invasive and aggressive pituitary tumor destroying the sella floor , responsible for suppurative meningitis ( sm ) in a 22-year - old man .
( a ) before bromocriptine ; ( b ) after treatment , bromocriptine intake and sm disappearance tumor size , hormonal assessment of our 4 patients , and bromocriptine dose used to reduce tumor volume and normalize prolactin .
cerebral mri showed an invasive and multidirectional pt measuring 47 mm  40 mm  30 mm destroying the sella floor and filling the sphenoid sinus [ figure 2 ] .
the pt was secreting prl [ table 1 ] . that one was normalized by bromocriptine and the tumor size was significantly reduced .
large invasive tumor destroying the sella floor , responsible for suppurative meningitis in a 49-year - old man .
( a ) before medical treatment ; ( b ) liquification of the tumor after bromocriptine a man aged 25 , with a history of chronic otitis and arrested puberty , was diagnosed as a multidirectional prolactinoma destroying the sella floor and measuring 30 mm  30 mm  30 mm [ figure 3 ] .
sm was sensitive to antibiotics . under dopamine agonists prl was normalized and the tumor volume decreased .
the pituitary tumor filling the sphenoid sinus before bromocriptine ( a ) and after bromocriptine ( b ) a 29-year - old man was sent to our unit for a prolactinoma revealed by epilepsy crises .
the pt was very large ( 68 mm  50 mm  50 mm ) and multidirectional with an extension to the chiasm , cavernous sinuses , posterior and nasal areas [ figure 4 ] .
after 3 months he had rhinorrhea , then one episode of sm sterilized by antibiotics . sm never relapsed after a follow - up of over 2 years .
mri showing a large tumor invading cavernous sinuses , the brain and sphenoid sinus ( a ) .
after dopamine agonists ( b ) the tumor size was reduced the table 1 shows tumor sizes , hormonal parameters and bromocriptine dose which was used to treat the 4 prolactinomas .
cerebral mri showed a pt invading cavernous sinuses , the sphenoid sinus and the brain [ figure 1 ] . hormonal assessment [ table 1 ] demonstrated high prl with gonadotroph deficit .
then , the pt was treated with dopamine agonists that were successful on prl ( 25 ng / ml ) and on tumor size [ figure 1 ] . after a follow - up of 7 years ,
invasive and aggressive pituitary tumor destroying the sella floor , responsible for suppurative meningitis ( sm ) in a 22-year - old man .
( a ) before bromocriptine ; ( b ) after treatment , bromocriptine intake and sm disappearance tumor size , hormonal assessment of our 4 patients , and bromocriptine dose used to reduce tumor volume and normalize prolactin .
the previous ones were proved in 1984 , 1988 and 1990 . clinical examination confirmed the meningeal syndrome and noticed rhinorrhea .
cerebral mri showed an invasive and multidirectional pt measuring 47 mm  40 mm  30 mm destroying the sella floor and filling the sphenoid sinus [ figure 2 ] .
the pt was secreting prl [ table 1 ] . that one was normalized by bromocriptine and the tumor size was significantly reduced .
large invasive tumor destroying the sella floor , responsible for suppurative meningitis in a 49-year - old man .
( a ) before medical treatment ; ( b ) liquification of the tumor after bromocriptine
a man aged 25 , with a history of chronic otitis and arrested puberty , was diagnosed as a multidirectional prolactinoma destroying the sella floor and measuring 30 mm  30 mm  30 mm [ figure 3 ] .
sm was sensitive to antibiotics . under dopamine agonists prl was normalized and the tumor volume decreased .
the pituitary tumor filling the sphenoid sinus before bromocriptine ( a ) and after bromocriptine ( b )
a 29-year - old man was sent to our unit for a prolactinoma revealed by epilepsy crises .
the pt was very large ( 68 mm  50 mm  50 mm ) and multidirectional with an extension to the chiasm , cavernous sinuses , posterior and nasal areas [ figure 4 ] .
after 3 months he had rhinorrhea , then one episode of sm sterilized by antibiotics .
mri showing a large tumor invading cavernous sinuses , the brain and sphenoid sinus ( a ) .
after dopamine agonists ( b ) the tumor size was reduced the table 1 shows tumor sizes , hormonal parameters and bromocriptine dose which was used to treat the 4 prolactinomas .
when it happens , it is usually observed in post - operative period or after tumor reduction by radiotherapy , apoplexy or medicine intake .
the situation is observed in people in whom meninges and sella floor are destroyed by an aggressive pt or an ectopic one arising from the skull base .
our 4 cases can be explained by the fact that prolactinomas are the largest and the most invasive pt , especially in males .
male prolactinomas often destroy the sellar floor and invade the sphenoid sinus , then the nasopharynx .
the meningeal and bony breaches lead to intra and extradural spaces communication , which is responsible for bacterial infection of meninges and encephalic structures .
the most difficult differential diagnosis with meningitis occurring in people with pt is pituitary apoplexy , which mimics perfectly bacterial meningitis symptoms .
however , a real microbial meningitis with or without rhinorrhea can be observed in apoplexy .
the true microbial meningitis secondary to pt is an exceptional phenomenon compared to pituitary apoplexy , which is relatively more frequent . to our best knowledge
only 15 sm , revealing pituitary adenomas or appearing under medical treatment have been reported so far .
csf leak may proceed or not sm , and can be totally unnoticed . according to lam et al . who analyzed 29 articles published between 1980 and 2011 there were only 52 pt with csf leak .
the seven cases were divided in two groups : the primitive meningitis or meningitis occurring prior to any treatment of the pt , and secondary meningitis occurring after surgery and/or dopamine agonists intake as in our 4 observation .
our personal research found 15 cases meningitis secondary to pt . if we add our 4 cases , one can totalize 19 cases . in this group
most pt were prolactinomas , especially males ones . among this group 14 were primitive .
secondary ones ( n = 5 ) appeared under medical treatment , preceded or not by surgery or radiotherapy .
sellar floor destruction was obvious on radiographies in all except one case [ table 2 ] .
their age ( varying between 22 and 69 years ) did not seem to be a determining factor , but the nature of the adenoma and sphenoid sinus invasion seem fundamental . according to ciatto and to lascelles et al .
we find only one case concerning gh adenoma treated by somatostatin 's analogs . a case of recurrent meningitis which appeared many years after neurosurgery was observed in nelson syndrome too .
curiously sm was not reported in mixed pt and gonadotroph adenomas which are usually very large and very invasive .
contrary to many authors and in agreement with ciatto , we think the association of pituitary adenoma and meningitis is more common than it is generally supposed as we observed it in nearly 5% of our male mprl .
so , one should think about it more often even if a cause of sm seems obvious from the first sight as in our 4 case who suffered from chronic otitis .
radiological research for pt should be systematic , especially if headaches , visual troubles , and gonadal abnormalities with or without anterior or posterior pituitary deficiencies are present .
physicians who deal with large pt should be aware of high risk spontaneous meningitis , but also of secondary sm which can appear 1 month to 4 years or even more after medical treatment initiation by dopamine agonists or somatostatin 's analogs or radiotherapy . on another hand
, medical treatment initiation should be gradual , especially for huge tumors as rapid shrinkage may lead to csf leak apparition .
if this situation appears , a medical solution may be tried using temporary lumbar puncture or a lumboperitoneal shunt until the bony defect is clogged by fibrosis .
if this attitude fails , surgical repair is recommended although the reparation may represent a great challenge because of the many potential sites of the csf around the tumor . if surgical repair in not feasible some authors recommend a vaccination against pathogens of the upper respiratory tract such as streptococcus pneumonia , haemophilus influenza and neisseria meningitidis to prevent sm .
three revealed the pt , and one was observed after medical treatment . in 2 cases
the described cases emphasize the necessity of an early diagnosis and treatment of large and invasive pt , especially male mprl . medical treatment , which is now the gold standard for prolactinomas ,
should be gradual and well monitored to avoid rhinorrhea or otorrhea which can lead to potentially fatal bacterial meningitis .
 background : suppurative meningitis ( sm ) or bacterial meningitis is a life - threatening condition , which is exceptionally due to pituitary tumors ( pt ) . our aim was to analyze its frequency among male macroprolactinomas ( mprl ) deemed to be aggressive , to report the cases we observed in our practice and describe the circumstances under which sm appeared.materials and methods : we retrospectively analyzed 82 male mprl in order to look for a history of well proved sm and the circumstances under which sm appeared . 
 we also took into account the possibility of sm relapsing.results:four out of 82 male mprl had sm = 4.87% . 
 three consulted for sm symptoms . 
 sm was confirmed in infectious diseases department , but only one had rhinorrhea . hormonal assessment and 
 cerebral magnetic resonance imaging pleaded for aggressive prolactinomas . 
 after antibiotics , sm was sterilized . 
 then , mprl were treated with bromocriptine , which normalized prolactin and reduced pt . 
 sm never relapsed . 
 the 4th case was hospitalized for a large multidirectional prolactinoma invading and/or arising from the skull base . 
 he was operated on 3 times and then he was given bromocriptine . 
 after 3 months , he had rhinorrhea and then sm which was successfully treated by antibiotics . 
 sm never relapsed after tumor reduction.conclusion:sm was demonstrated in 4.87% . 
 sm has revealed mprl in 3 cases and appeared after bromocriptine intake in the 4th one . 
 endocrinologists should be aware of this severe condition , which can be avoided by repairing as soon as possible the bony defect secondary to aggressive tumors , unless it is clogged by fibrosis : what probably happened in our cases . 
I
M
R
C
Case 1
Case 2
Case 3
Case 4
D
C