Nonfunctioning pituitary macroadenomas : treatment and long-term follow-up
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(2) 4HE NATURAL COURSE OF NONFUNCTIONING PITUITARY MACROADENOMAS IN NON OPERATED PATIENTS. /- $EKKERS
(3) 3 (AMMER
(4) 2*7 DE +EIZER
(5) & 2OELFSEMA
(6) 0* 3CHUTTE
(7) *7! 3MIT
(8) *! 2OMIJN
(9) !- 0EREIRA . $EPARTMENT OF %NDOCRINOLOGY AND -ETABOLIC $ISEASES
(10) /PHTALMOLOGY AND . .EUROSURGERY
(11) ,EIDEN 5NIVERSITY -EDICAL #ENTER
(12) ,EIDEN
(13) 4HE .ETHERLANDS 3UBMITTED. $)"15&3.
(14) 46.."3: /BJECTIVE 4HE NATURAL HISTORY OF NONFUNCTIONING PITUITARY MACROADENOMAS .&-! HAS NOT BEEN FULLY ELUCIDATED 4HEREFORE
(15) WE EVALUATED PITUITARY FUNCTION
(16) VISUAL lELDS AND TUMOR SIZE DURING LONG TERM FOLLOW UP OF NON OPERATED PATIENTS WITH .&-! $ESIGN &OLLOW UP STUDY 0ATIENTS 4WENTY EIGHT PATIENTS AGE ¢ YEARS WITH .&-!
(17) NOT OPERATED AFTER INITIAL DIAGNOSIS
(18) WERE INCLUDED 2ESULTS )NITIAL PRESENTATION WAS PITUITARY INSUFlCIENCY IN
(19) VISUAL lELD DEFECTS IN
(20) APOPLEXY IN
(21) AND CHRONIC HEADACHE IN OF THE PATIENTS 4HE DURATION OF FOL LOW UP WAS ¢ MONTHS 2ADIOLOGICAL EVIDENCE OF TUMOR GROWTH WAS OBSERVED IN OF PATIENTS AFTER DURATION OF FOLLOW UP OF ¢ MONTHS 3IX PATIENTS WERE OPERATED
(22) BECAUSE TUMOR GROWTH WAS ACCOMPANIED BY VISUAL lELD DEFECTS 6ISUAL IMPAIRMENTS IMPROVED IN ALL CASES AFTER TRANSSPHENOIDAL SURGERY 3PONTANEOUS REDUC TION IN TUMOR VOLUME WAS OBSERVED IN PATIENTS .O INDEPENDENT PREDICTORS FOR INCREASE OR DECREASE IN TUMOR VOLUME COULD BE FOUND BY REGRESSION ANALYSIS #ONCLUSION /BSERVATION ALONE IS A SAFE ALTERNATIVE FOR TRANSSPHENOIDAL SURGERY IN SE $IBQUFS. LECTED .&-! PATIENTS
(23) WITHOUT THE RISK OF IRREVERSIBLY COMPROMISING VISUAL FUNCTION. .
(24) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. */530%6$5*0/ .ONFUNCTIONING PITUITARY MACROADENOMAS .&-! ARE THE MOST PREVALENT PITUITARY MACROADENOMAS
(25) !LTHOUGH .&-!S ARE BENIGN IN ORIGIN
(26) MASS EFFECTS MAY LEAD TO SERIOUS CLINICAL SYMPTOMS SUCH AS VISUAL IMPAIRMENTS
(27) CHRONIC HEADACHE AND PITUITARY INSUFlCIENCY !T THE TIME OF INITIAL DIAGNOSIS
(28) VISUAL lELD DEFECTS ARE DETECTED IN OF .&-! PATIENTS 4RANSSPHENOIDAL SURGERY IS THE TREATMENT OF CHOICE IN .&-! PATIENTS WITH VISUAL lELD DEFECTS 4HE MAIN AIM OF SURGICAL TREATMENT IS IMPROVEMENT OF VISUAL FUNCTION
(29) WHICH IS ACHIEVED IN OVER OF CASES
(30) 3TUDIES ON THE EFFECT OF SURGERY IN .&-! ON PITUITARY FUNCTION SHOW CONmICTING RESULTS 3OME STUDIES REPORT
(31) TO A VARIABLE DEGREE
(32) AN IMPROVEMENT IN PITUITARY FUNCTION
(33)
(34) WHEREAS OTHERS COULD NOT DEMONSTRATE SIGNIlCANT IMPROVEMENT IN PITUITARY FUNCTION
(35) OR EVEN SHOWED DECREASED PITUITARY FUNCTION AFTER TRANSSPHENOIDAL SURGERY
(36)
(37)
(38) 4RANSSPHENOIDAL SURGERY LEADS TO LONG TERM TUMOR CONTROL IN ^ OF PATIENTS
(39)
(40) AND
(41) IN SELECTED SERIES
(42) IN EVEN MORE THAN OF THE PATIENTS
(43) 4HE NATURAL COURSE OF .&-! IS LARGELY UNKNOWN
(44) BECAUSE THE MAJORITY OF PATIENTS WITH .&-! ARE OPERATED 4HE NATURAL COURSE OF PITUITARY INCIDENTALOMAS WAS REPORTED IN PREVIOUS REPORTS
(45) )N OF THESE REPORTS
(46) DATA ON THE NATURAL COURSE OF .&-! WERE REPORTED
(47)
(48)
(49) 4HE lFTH STUDY DESCRIBED THE COMBINED DATA OF BOTH NONFUNCTION ING MICROADENOMAS AND MACROADENOMAS
(50) NOT PERMITTING A CONCLUSION WITH RESPECT TO THE NATURAL COURSE OF .&-! PER SE 4HOSE STUDIES
(51) WITH A FOLLOW UP PERIOD RANGING FROM TO MONTHS
(52) SHOW AN INCREASE IN TUMOR SIZE RANGING FROM TO OF ALL PATIENTS WITH .&-! 4HE NATURAL COURSE OF .&-! PRESENTING FOR OTHER REASONS THAN THE PRESENCE OF AN INCIDENTALOMA IS UNCLEAR 4HE MAIN INDICATION FOR SURGERY IN PATIENTS WITH .&-! IN OUR HOSPITAL IS THE PRESENCE OF VISUAL IMPAIRMENT )N THE ABSENCE OF VISUAL lELD DEFECTS
(53) THE INITIAL THERAPEUTIC APPROACH IS TO EVALUATE TUMOR GROWTH AND VISUAL FUNCTION WITH REGULAR INTERVALS )N PATIENTS WITH ONLY MINIMAL VISUAL lELD DEFECTS SURGERY IS DEFERRED 4HE AIM OF THE PRESENT STUDY WAS TO EVALUATE CHANGES IN PITUITARY FUNCTION
(54) VISUAL FUNCTION AND TUMOR SIZE DURING LONG TERM FOLLOW UP OF THESE NON OPERATED PATIENTS WITH .&-! . 1"5*&/54"/%.&5)0%4 "ETWEEN AND
(55) CONSECUTIVE PATIENTS WERE DIAGNOSED WITH .&-! AT THE ,EIDEN 5NIVERSITARY -EDICAL #ENTER 0ATIENTS WERE INCLUDED IN THIS STUDY BASED ON THE FOLLOWING CRITERIA -ACROADENOMA ON -2 IMAGING !BSENCE OF ANY CLINICAL AND BIOCHEMICAL SIGNS OF HORMONE EXCESS . .
(56) ! PROLACTIN LEVEL BELOW «G, TO EXCLUDE POSSIBLE PROLACTINOMAS
(57) %XPECTATIVE APPROACH AFTER INITIAL DIAGNOSIS !T LEAST TWO SEQUENTIAL -2)S TO EVALUATE TUMOR GROWTH 4HE VAST MAJORITY OF THE PATIENTS N
(58) WAS OPERATED AFTER DIAGNOSIS )N PATIENTS INITIALLY AN EXPECTATIVE APPROACH WAS UNDERTAKEN AFTER DIAGNOSIS .INE OF THESE PATIENTS WERE NOT ELIGIBLE FOR THE PRESENT STUDY
(59) FOR THE FOLLOWING REASONS FOLLOW UP BY #4 SCAN ONLY N
(60) LOST TO FOLLOW UP N
(61) NO FOLLOW UP BY -2) BECAUSE OF VERY HIGH AGE AND THE ABSENCE OF VISUAL lELD DEFECTS N
(62) FOLLOW UP PERIOD SHORTER THAN ONE YEAR N #ONSEQUENTLY
(63) A TOTAL OF PATIENTS WAS INCLUDED IN THIS STUDY 4HE DURATION OF FOLLOW UP WAS DElNED AS THE INTERVAL BETWEEN THE lRST AND THE LAST -2) SCAN "ECAUSE THE STUDY WAS DESIGNED TO ASSESS THE NATURAL COURSE OF .&-!S
(64) IN CASE OF AN OPERATION FOR .&-!
(65) THE LAST -2) BEFORE SURGERY WAS ASSIGNED AS THE END OF FOLLOW UP !N EXPERIENCED ENDOCRINOLOGIST SAW EACH PATIENT
(66) AT LEAST TWICE A YEAR 'ROWTH HOR MONE '( DElCIENCY WAS DElNED AS AN )'& LEVEL BELOW THE REFERENCE RANGE FOR AGE AND SEX
(67) ANDOR AN INSUFlCIENT RISE IN '( LEVELS ABSOLUTE VALUE «G, AFTER STIMULATION DURING AN INSULIN TOLERANCE TEST )44 "EFORE
(68) SERUM '( WAS MEASURED BY 2)! "IOLABSERONO
(69) #OINSINS
(70) 3WITZERLAND 4HE 2)! WAS CALIBRATED AGAINST 7(/ $IBQUFS. )20
(71) WITH AN INTERASSAY VARIATION COEFlCIENT BELOW &ROM ONWARDS '( . . WAS MEASURED BY IMMUNOmUOROMETRIC ASSAY 7ALLAC
(72) 4URKU
(73) &INLAND
(74) CALIBRATED AGAINST 7(/ )20
(75) WITH AN INTERASSAY VARIATION COEFlCIENT OF BETWEEN AND «G, )'& DETERMINATION WAS PERFORMED BY 2)! AVAILABLE SINCE ).#34!2 #ORP
(76) 3TILLWATER
(77) -.
(78) WITH AN INTERASSAY VARIATION LESS THAN !#4( DElCIENCY WAS DElNED AS A BASAL CORTISOL LEVEL AT !- OF «MOLL ANDOR AN INSUFlCIENT INCREASE IN CORTISOL LEVELS ABSOLUTE VALUE «MOL L AFTER AN INSULIN TOLERANCE TEST )44 NADIR GLUCOSE NMOL, )N TWO PATIENTS
(79) AN )44 WAS CONTRAINDICATED AND A CORTICOTROPHIN RELEASING HORMONE #2( STIMULATION TEST WAS PERFORMED
(80) USING HUMAN #2(
(81) IN WHICH WE USED THE SAME CUT OFF LEVELS FOR CORTISOL CONCENTRATIONS LIKE IN THE )44 #ORTISOL WAS MEASURED WITH THREE DIFFERENT IMMUNOASSAYS OVER TIME 5NTIL CORTISOL WAS MEASURED BY IN HOUSE 2)! WITH AN INTERASSAY COEFlCIENT OF VARIATION OF "ETWEEN AND A mUORESCENCE ENERGY TRANSFER IMMUNOASSAY 3YVA !DVANCE 3YVA #OMPANY
(82) 0ALO !LTO
(83) #! WAS USED
(84) WITH AN INTERASSAY VARIATION COEFlCIENT OF TO &ROM CORTISOL WAS MEASURED BY mUORESCENCE POLARISATION ASSAY ON A 4$X !BBOTT
(85) !BBOTT 0ARK
(86) )LL 4HE INTERASSAY VARIATION COEFlCIENT IS ABOVE «MOLL AND AMOUNTS TO UNDER «MOLL )N ADDITION
(87) THE BIANNUAL EVALUATION CONSISTED OF MEASUREMENT OF FREE 4
(88) ,(&3( ALL PATIENTS
(89) ESTRADIOL PREMENOPAUSAL FEMALE PATIENTS
(90) AND TESTOSTERONE MALE PATIENTS CONCENTRATIONS 0ROLACTIN WAS MEASURED WITH A SENSITIVE TIME RESOLVED mUORO IMMUNOASSAY 7ALLAC
(91) 4URKU
(92) &INLAND
(93) CALIBRATED AGAINST 7(/ RD )NTERNATIONAL 3TANDARD FOR 0ROLACTIN 4HE INTERASSAY COEFlCIENT OF VARIATION WAS TO IN THE ASSAY RANGE FROM TO «G, .
(94) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. 4HE EVALUATION OF VISUAL FUNCTION WAS DONE BY AN OPHTHALMOLOGIST
(95) AND INCLUDED VI SUAL ACUITY
(96) PUPILLARY FUNDUS AND VISUAL lELDS 6ISUAL lELDS WERE ASSESSED BY (UMPHREY PERIMETRY IN ALL PATIENTS 'OLDMAN PERIMETRY WAS USED AS AN ADDITIONAL TOOL TO ASSESS PERIPHERAL VISUAL lELD DEFECTS /PHTALMOLOGIC ASSESSMENT WAS PERFORMED AT BASELINE
(97) AFTER SIX MONTHS AND SUBSEQUENTLY AT YEARLY INTERVALS 6ISUAL lELD DEFECTS WERE CLASSIlED AS MINIMAL IF THERE WAS A SMALL DEFECT IN ONLY ONE EYE IN ONLY ONE QUADRANT 2EPEAT -2) WAS PERFORMED WITHIN ONE YEAR AFTER THE INITIAL DIAGNOSIS )F NO GROWTH WAS OBSERVED
(98) SUBSEQUENT -2) SCANNING WAS PERFORMED EVERY SECOND YEAR 4HE FOLLOW UP OF THE PATIENTS WAS PART OF REGULAR MEDICAL CARE 4HE APPROACHES DE SCRIBED IN THIS PAPER DID NOT INVOLVE ANY RANDOMIZATION OR ANY EXPERIMENTAL INTERVENTION !CCORDING TO $UTCH LAW
(99) EACH PATIENT HAS TO BE FULLY INFORMED ON THE PROS AND CONTRAS OF EACH TREATMENT STRATEGY
(100) AND EACH PATIENT CAN ONLY BE TREATED AFTER GIVING ORAL INFORMED CONSENT . "TTFTTNFOUPGSBEJPMPHJDBMJNBHJOH 4WO OBSERVERS EVALUATED ALL -2) SCANS
(101) INDEPENDENTLY OF EACH OTHER 4UMOR VOLUME WAS ASSESSED BY MEASURING THE LARGEST DIAMETER OF THE TUMOR IN THREE DIRECTIONS 4HE VERTICAL DIAMETER 6 WAS MEASURED ON SAGITTAL 4 WEIGHTED AND CORONAL 4 WEIGHTED SCANS
(102) ANTEROPOSTERIOR !0 DIAMETER ON CORONAL 4 WEIGHTED SCANS AND TRANSVERSAL DIAMETER 4 ON 4 WEIGHED SAGITTAL SCANS )MAGING WAS PERFORMED ON -2 SCANNERS WITH DIFFERENT lELD STRENGTHS
(103) RANGING FROM 4ESLA TO 4ESLA )MAGING PARAMETERS INCLUDED THE FOLLOWING ! lELD OF VIEW &/6 OF MM AND A MATRIX SIZE OF X MM
(104) YIELDING AN IN PLANE SPATIAL RESOLUTION OF X MM SCAN DURATION WAS INCREASED AT LOWER lELD STRENGTHS IN ORDER TO MAINTAIN SUFlCIENT RESOLUTION 4UMOR VOLUME ASSESSMENT WAS NOT PERFORMED BY THE SAME -2) SCANNER IN EACH PATIENT
(105) BECAUSE THE HIGHER STRENGTH -2)S WERE NOT AVAILABLE DURING THE INITIAL PART OF THE OBSERVATION PERIOD OF THE PRESENT STUDY 4UMOR GROWTH WAS DElNED AS AN INCREASE IN TUMOR SIZE ON -2) OF MORE THAN ONE MIL LIMETER IN ANY DIRECTION
(106) INDEPENDENT OF THE DEVELOPMENT OF VISUAL lELD DEFECTS 4UMOR VOLUME WAS ASSESSED AS THE VOLUME OF A ROTATING ELLIPSOID
(107) WITH THE FOLLOWING FORMULA / 6X!0X4 . 4UBUJTUJDT "INARY LOGISTIC REGRESSION WAS PERFORMED TO ASSESS PREDICTORS FOR INCREASE OR DECREASE IN TUMOR GROWTH !LL DATA ARE EXPRESSED AS MEAN ¢ STANDARD ERROR
(108) UNLESS OTHERWISE MEN TIONED ! P VALUE OF WAS CONSIDERED STATISTICALLY SIGNIlCANT . .
(109) 3&46-54. 1BUJFOUDIBSBDUFSJTUJDT 5BCMF. 4WENTY EIGHT PATIENTS WERE INCLUDED -EAN AGE AT PRESENTATION WAS ¢ YEARS 4HE DURATION OF FOLLOW UP WAS MONTHS ¢ MONTHS )NITIAL PRESENTATIONS WERE PITUITARY IN SUFlCIENCY IN
(110) VISUAL lELD DEFECTS IN
(111) APOPLEXY IN
(112) AND CHRONIC HEADACHE IN OF THE PATIENTS )N ONLY PATIENTS THE MACROADENOMA WAS AN INCIDENTAL lNDING 2ADIOLOGICAL IMAGING REVEALED A MACROADENOMA IN ALL CASES
(113) WITH SUPRASELLAR EXTENSION IN ANDOR LATERALINFRASELLAR EXTENSION IN OF CASES ! LARGE NUMBER OF PATIENTS HAD PITUITARY INSUFlCIENCY OF ONE OR MORE AXIS 6ISUAL lELD DEFECTS WERE PRESENT IN PATIENTS AT INITIAL PRESENTATION )N OF THESE PATIENTS THE DEFECTS WERE CLASSIlED AS MINIMAL 6ISUAL ACUITY WAS NORMAL IN OF PATIENTS WITH MORE THAN MINIMAL VISUAL lELD DEFECTS . $IBQUFS. 4ABLE 0ATIENT CHARACTERISTICS AT INITIAL PRESENTATION N . . .BMF'FNBMF. . "HFBUEJBHOPTJT ZFBST. . *OJUJBM1SFTFOUBUJPO 1JUVJUBSZEFmDJFODZ. . *ODJEFOUBMPNB. . 7JTVBMmFMEEFGFDUT. . )FBEBDIF. . "QPQMFYJB. . 1JUVJUBSZGVODUJPO *OUBDUGVODUJPOPGBOUFSJPSQJUVJUBSZHMBOE. . 4JOHMFQJUVJUBSZEFmDJFODZ. . .VMUJQMFQJUVJUBSZEFmDJFODJFT. . 1BOIZQPQJUVJUBSJTN. . 1SPMBDUJO H- JONBMFQBUJFOUT NFEJBO
(114) SBOHF . SBOHF. 1SPMBDUJO H- JOGFNBMFQBUJFOUT NFEJBO
(115) SBOHF. SBOHFUP. *('4%TDPSF NFEJBO
(116) SBOHF. SBOHFUP. .3*DIBSBDUFSJTUJDT 5VNPSWPMVNF NN. . 4VQSBTFMMBSFYUFOTJPO. . -BUFSBMJOGSBTFMMBSFYUFOTJPO. . 7JTVBMmFMEFWBMVBUJPO /PWJTVBMmFMEEFGFDUT. . .JOJNBMWJTVBMmFMEEFGFDUT. . #JUFNQPSBMWJTVBMmFMEEFGFDUT. .
(117) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. 5SFBUNFOUTUSBUFHZ &IFTEEN OF THE PATIENTS WHERE NOT OPERATED BECAUSE THEY DID NOT HAVE ANY VISUAL lELD DEFECTS )N OTHER PATIENTS A CONSERVATIVE APPROACH WAS CHOSEN
(118) BECAUSE THEY HAD ONLY MINIMAL VISUAL lELD DEFECTS 3EVEN PATIENTS WERE NOT OPERATED DESPITE VISUAL lELD DEFECTS FOR THE FOLLOWING REASONS 4HE PATTERN OF THE VISUAL lELD DEFECTS WAS NOT COMPATIBLE WITH THE DIAGNOSIS OF CHIASM COMPRESSION
(119) AND THERE WAS A MORE LIKELY OPHTHALMOLOGIC EXPLA NATION OF THE DEFECTS . )N OTHER PATIENTS
(120) ONE OF WHICH HAD DECREASED VISUAL ACUITY
(121) SURGICAL TREATMENT WAS CONTRAINDICATED BECAUSE OF HIGH AGE
(122) AND SERIOUS CO MORBIDITY &INALLY
(123) IN PATIENTS WITH VISUAL lELD DEFECTS AND PITUITARY APOPLEXY AN INITIAL EXPECTATIVE APPROACH WAS CHOSEN )N ALL SUBJECTS A WAIT AND SEE APPROACH WAS CHOSEN WITH CAREFUL FOLLOW UP OF THE VISUAL FUNCTION. 3BEJPMPHJDBMGPMMPXVQ !LL PATIENTS HAD AT LEAST TWO -2) SCANS
(124) WITH A MEAN INTERVAL BETWEEN THE lRST AND THE LAST -2) OF ¢ MONTHS 2ADIOLOGICAL EVIDENCE OF TUMOR GROWTH WAS OBSERVED IN OF PATIENTS
(125) AFTER A DURATION OF FOLLOW UP OF ¢ MONTHS 4ABLE )N THESE PATIENTS
(126) THE MEAN TUMOR VOLUME INCREASED FROM MM ¢ MM TO MM ¢ MM 4HE MEAN INCREASE IN TUMOR SIZE
(127) ESTIMATED BY THE GROWTH IN THE DIAMETER WITH THE LARGEST GROWTH
(128) WAS MMYEAR 'ROWTH VELOCITY
(129) EXPRESSED IN MM
(130) WAS MMYEAR )F WE EXCLUDE THE PATIENTS WITH APOPLEXY AT INITIAL PRESENTATION
(131) BECAUSE IN . 4ABLE #HARACTERISTICS OF PATIENTS WITH TUMOR ENLARGEMENT N . "HFBUEJBHOPTJT. 'FNBMFNBMF. 'PMMPXVQ NPOUIT. 5VNPSWPMVNFBUEJBHOPTJT NN. 5VNPSWPMVNFFOEGPMMPXVQ NN. . '. . . . . '. . . . . '. . . . . '. . . . . '. . . . . '. . . . . .. . . . . .. . . . . .. . . . . .. . . . . .. . . . . .. . . . . .. . . . . .. . . . . . . . .
(132) THESE CASES SUBSEQUENT TUMOR ENLARGEMENT IS LESS PROBABLE
(133) AN INCREASE IN TUMOR VOLUME WAS OBSERVED IN OF THE REMAINING PATIENTS DURING PROLONGED FOLLOW UP 2EMARKABLY
(134) REDUCTION IN TUMOR VOLUME WAS OBSERVED IN PATIENTS )N THOSE PATIENTS TUMOR VOLUME DECREASED FROM MM ¢ MM TO MM ¢ MM 4WO OF THOSE PATIENTS INITIALLY PRESENTED WITH PITUITARY APOPLEXY )N THE REMAINING PATIENTS MEAN TUMOR VOLUME MM ¢ MM NO CHANGE IN TUMOR VOLUME COULD BE DETECTED BY -2) )N ONE PATIENT
(135) DESPITE A FOLLOW UP PERIOD OF MONTHS
(136) NO TUMOR GROWTH COULD BE OBSERVED "INARY LOGISTIC REGRESSION WAS PERFORMED IN A MODEL INCLUDING INCREASE AND DECREASE IN TUMOR VOLUME AS DEPENDENT VARIABLE AND AGE
(137) GENDER
(138) TUMOR VOLUME
(139) TUMOR EXTEN SION
(140) HYPOPITUITARISM
(141) PROLACTIN LEVELS AND FOLLOW UP DURATION AS INDEPENDENT VARIABLES .O INDEPENDENT PREDICTORS FOR INCREASE OR DECREASE IN TUMOR VOLUME COULD BE FOUND BY REGRESSION ANALYSIS. 0QIUIBMNPMPHJDGPMMPXVQ )N OF THE PATIENTS
(142) TUMOR GROWTH ON -2) WAS ASSOCIATED WITH INCREASED DEFECTS OF VISUAL lELDS )N OF THOSE PATIENTS THE VISUAL lELD DEFECTS WERE LIKELY CAUSED BY TUMOR $IBQUFS. MASS EFFECT )N THE TWO OTHER PATIENTS
(143) ONE WITH GLAUCOMA AND ONE WITH UVEITIS
(144) THE . . PREDOMINANT DEFECTS WERE NOT IN THE UPPER TEMPORAL QUADRANT )N PATIENTS WITH TUMOR GROWTH NO VISUAL lELD DEFECTS COULD BE DETECTED )N ONE PATIENT
(145) WHO HAD ONLY MINIMAL VISUAL lELD DEFECTS
(146) THERE WAS NO INCREASE IN VISUAL lELD DEFECTS )N OF THE PATIENTS WITH A DECREASE IN TUMOR VOLUME ON -2)
(147) AN IMPROVEMENT OF VISUAL DEFECTS COULD BE OBSERVED &OUR PATIENTS HAD APOPLEXY AS PRESENTING SYMPTOM
(148) ACCOMPANIED BY VISUAL lELD DE FECTS IN OF THEM )N ALL THESE THREE PATIENTS VISUAL lELDS NORMALIZED SPONTANEOUSLY WITHIN THREE MONTHS. &OEPDSJOFGPMMPXVQ )N OF THE PATIENTS WITH GROWING TUMORS ON -2)
(149) AN INCREASE IN PITUITARY DElCIENCIES WAS OBSERVED
(150) WHEREAS IN THE OTHER PATIENTS PITUITARY FUNCTIONS REMAINED STABLE )N ONLY ONE OF THE PATIENTS WITH A DECREASE IN TUMOR SIZE
(151) THERE WAS AN IMPROVEMENT OF PITUITARY FUNCTION )N OF THE PATIENTS WITH PITUITARY APOPLEXY
(152) INITIAL PITUITARY DElCIENCIES WERE PRESENT IN OF AXIS
(153) INCLUDING !#4( DElCIENCY )N THIS PATIENT PITUITARY DElCIENCIES RESOLVED WITHIN THREE MONTHS 4HE OTHER PATIENTS PRESENTED WITH APOPLEXY HAD NORMAL PITUITARY FUNCTION.
(154) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. &IGURE ,ONG TERM OUTCOME AFTER EXPECTATIVE APPROACH FOR .&-!. SDWLHQWV. 7XPRUJURZWK Q
(155) . 'HFUHDVHLQWXPRUVL]H DSRSOH[\QRQ DSRSOH[\\HVQ
(156) . 7UDQVVSKHQRLGDOVXUJHU\ Q
(157). ([SHFWDWLYHDSSURDFK Q
(158). 6WDEOHWXPRUVL]H DSRSOH[\QRQ DSRSOH[\\HVQ
(159) . ,PSURYHPHQWLQYLVXDOILHOG GHIHFWV Q
(160) . -POHUFSNPVUDPNF 'JHVSF. 4HE MEAN FOLLOW UP PERIOD WAS ¢ MONTHS !T THE END OF FOLLOW UP
(161) IN PATIENTS WITHOUT SIGNS OF TUMOR GROWTH ON -2)
(162) THERE WAS STILL NO INDICATION FOR SURGERY 3IX PATIENTS WERE OPERATED
(163) BECAUSE TUMOR GROWTH WAS ACCOMPANIED BY VISUAL lELD DEFECTS !FTER TRANSSPHENOIDAL SURGERY
(164) VISUAL lELD DEFECTS IMPROVED IN THESE PATIENTS )N OTHER PATIENTS WITH TUMOR GROWTH
(165) THE CONSERVATIVE APPROACH WAS CONTINUED BECAUSE OF NORMAL VISUAL lELDS N
(166) OR
(167) STABLE
(168) MINIMAL VISUAL lELD DEFECTS N 4HREE PATIENTS WITH TUMOR GROWTH AND VISUAL lELD DEFECTS WERE NOT OPERATED
(169) BECAUSE OF NON COMPATIBILITY OF THE DEFECTS WITH COMPRESSION OF THE OPTIC CHIASM BY .&-! N
(170) OR HIGH AGE AND ASSOCIATED CO MORBIDITY N )N THE LAST PATIENT VISUAL lELD DEFECTS WERE ACCOMPANIED BY A SLIGHT DECREASE IN VISUAL ACUITY . %*4$644*0/ )N THIS STUDY WE EVALUATED THE NATURAL COURSE OF .&-! )N .&-! PATIENTS
(171) WITH A MEAN FOLLOW UP PERIOD OF MORE THAN YEARS
(172) TUMOR GROWTH WAS OBSERVED IN PATIENTS . .
(173) 4ABLE 4HE NATURAL COURSE OF TUMOR VOLUME IN NONFUNCTIONING PITUITARY MACROADENOMAS. "VUIPS. .BDSPBEFOPNB. .FBOGPMMPXVQ. *ODSFBTFJO UVNPSWPMVNF. %FDSFBTFJO UVNPSWPMVNF. 'FMELBNQFUBM . / . NPOUIT. / . / . %POPWBOFUBM . / . NPOUIT. / . / . 3FJODLFFUBM . / . NPOUIT. / . / . 4BOOPFUBM . / B. NPOUIT. / . / . "SJUBFUBM . / . NPOUIT. / . / . 1SFTFOUTFSJFT. / . NPOUIT. / . / . A. #ONSISTING OF BOTH NONFUNCTIONING PITUITARY MICROADENOMAS AND MACROADENOMAS. )N OF THESE PATIENTS
(174) TUMOR GROWTH WAS ACCOMPANIED BY INCREASED VISUAL lELD DEFECTS
(175) LIKELY TO BE CAUSED BY MASS EFFECTS OF THE TUMOR 3URGICAL INTERVENTION WAS PERFORMED IN ONLY N OF ALL PATIENTS
(176) AND IMPROVED VISUAL lELDS IN ALL CASES 2EMARKABLY
(177) A SPONTANEOUS DECREASE IN TUMOR VOLUME WAS OBSERVED IN OF THE PATIENTS DURING LONG TERM FOLLOW UP 4HUS
(178) IN THE ABSENCE OF VISUAL IMPAIRMENTS
(179) OBSERVATION ALONE IS A SAFE ALTERNATIVE FOR SURGERY IN SELECTED PATIENTS WITH .&-!
(180) SINCE SURGERY CAN ULTIMATELY BE WITHHELD IN THE MAJORITY OF THESE PATIENTS
(181) WITHOUT COMPROMISING VISUAL lELD DEFECTS $IBQUFS. 4O DATE
(182) ONLY STUDIES REPORTED THE NATURAL COURSE OF .&-!
(183) DISCOVERED AS INCIDENTALO. . MAS
(184) COMPRISING A TOTAL OF PATIENTS
(185)
(186)
(187)
(188) WHEREAS AN ADDITIONAL STUDY REPORTED THE NATURAL COURSE OF A COMBINED SERIES OF BOTH NONFUNCTIONING MICRO AND MACROAD ENOMAS 4HOSE STUDIES
(189) SUMMARIZED IN 4ABLE
(190) WITH A FOLLOW UP PERIOD OF MONTHS
(191) REPORT AN INCREASE IN TUMOR SIZE IN ABOUT OF THE PATIENTS (OWEVER
(192) SEVERAL ASPECTS OF THE DESIGN OF THE PRESENT STUDY WERE DIFFERENT FROM THOSE PREVIOUS STUDIES 7E INCLUDED ALL .&-! PATIENTS
(193) IN WHOM SURGERY WAS NOT PERFORMED FOR ANY REASON )N CON TRAST TO THESE PREVIOUS STUDIES
(194) AN INCIDENTALOMA WAS THE INITIAL lNDING IN ONLY A MINORITY OF OUR PATIENTS 4HEREFORE
(195) THE CHARACTERISTICS OF OUR STUDY POPULATION ARE DIFFERENT
(196) WITH A HIGHER PREVALENCE OF PITUITARY INSUFlCIENCY AND VISUAL lELD DEFECTS THAN THOSE IN THE PREVIOUS STUDIES
(197) 0REVIOUS STUDIES ALSO SHOWED THAT TUMOR GROWTH DOES NOT INVARIABLE LEAD TO VISUAL lELD DEFECTS
(198)
(199)
(200) )N OUR SERIES TUMOR GROWTH N WAS ACCOMPANIED BY VISUAL lELD DEFECTS IN ONLY PATIENTS -OREOVER
(201) IN ONLY OF THESE PATIENTS THE PATTERN WAS COMPATIBLE WITH TUMOR MASS EFFECT )N ALL PATIENTS OPERATED FOR TUMOR GROWTH AND VISUAL lELD DEFECTS
(202) THESE DEFECTS IMPROVED OR NORMALIZED 4HESE DATA SUGGEST THAT IN CASE OF THE DEVELOPMENT OF VISUAL lELD DEFECTS IN THE COURSE OF .&-!
(203) SURGICAL OUTCOME STILL IS FAVOURABLE WITH RESPECT TO VISUAL lELD DEFECTS 4HESE RESULTS ARE IN ACCORDANCE WITH OBSERVATIONS IN SURGICAL SERIES
(204) WHICH DOCUMENTED IMPROVEMENT OF VISUAL lELD DEFECTS IN OF .&-! PATIENTS AFTER TRANSSPHENOIDAL SURGERY
(205) )N PITUITARY MICROADENOMAS IN GENERAL
(206) TUMOR GROWTH IS OBSERVED IN ONLY A MINOR ITY OF THE PATIENTS
(207) IN CONTRAST TO .&-! -OREOVER
(208) IN MICROADENOMAS
(209) THE CHANCE OF .
(210) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. TUMOR GROWTH SEEMS TO BE ALMOST OUTWEIGHED BY THE CHANGE OF A DECREASE IN TUMOR SIZE
(211) )N PATIENTS WITH .&-! THE TUMOR ALREADY HAS DEMONSTRATED A PROPENSITY FOR GROWTH .ONETHELESS
(212) AFTER A MEAN FOLLOW UP PERIOD OF MONTHS NO TUMOR GROWTH COULD BE DETECTED IN THIS STUDY IN OF CASES (OWEVER
(213) AT INITIAL PRESENTATION
(214) THE RATE OF TUMOR GROWTH CANNOT BE PREDICTED IN INDIVIDUAL PATIENTS )N OUR STUDY
(215) NO INDEPENDENT PREDICTORS FOR INCREASE OR DECREASE IN TUMOR VOLUME COULD BE FOUND BY BINARY LOGISTIC REGRESSION )N PATIENTS WITH .&-!
(216) IT IS A REASONABLE APPROACH TO REPEAT -2 IMAGING ONE YEAR AFTER INITIAL DIAGNOSIS
(217) IN ORDER TO MAKE A lRST ESTIMATION OF TUMOR GROWTH )N OUR STUDY
(218) IN PATIENTS WITH TUMOR GROWTH
(219) THE MEAN INCREASE IN DIAMETER WAS ONLY MMYEAR
(220) WHICH IS BELOW THE DETECTION LIMIT OF -2) 4HESE DATA SUGGEST THAT
(221) FOR FURTHER FOLLOW UP
(222) AN APPROACH WITH A REPEAT -2) EVERY SECOND YEAR IS SAFE AND OPTIMAL FOR DETECTION OF POSSIBLE TUMOR GROWTH $IAGNOSTIC ACCURACY MIGHT BE A LIMITATION OF THIS STUDY
(223) BECAUSE
(224) IN STRICT SENSE
(225) PITUITARY ADENOMA IS A HISTOPATHOLOGICAL DIAGNOSIS AND A NUMBER OF OTHER SELLAR LESIONS MAY MIMIC PITUITARY ADENOMAS
(226) SUCH AS GERMINOMAS
(227) CRANIOPHARYNGIOMAS
(228) MENINGIOMAS
(229) SARCOIDOSIS AND LYMPHOCYTIC INlLTRATION (OWEVER
(230) THERE ARE
(231) IN ADDITION TO THE ABSENCE OF HOR MONE OVERPRODUCTION
(232) ARGUMENTS THAT IN OUR SERIES THE VAST MAJORITY OF THE LESIONS CONSIST OF .&-! )N AUTOPSY SERIES PITUITARY LESIONS TURN OUT TO BE NONFUNCTIONING ADENOMAS IN ABOUT
(233) THE OTHER MAINLY BEING HORMONAL ACTIVE ADENOMAS
(234) -OREOVER
(235) IN THE VAST MAJORITY OF PATIENTS
(236) -2) CAN WITH ADEQUATE ACCURACY DIFFERENTIATE BETWEEN PITUITARY ADENOMAS AND CRANIOPHARYNGIOMAS
(237)
(238) AND BETWEEN PITUITARY ADENOMA AND PITUITARY HYPERTROPHY 4HE POSSIBILITY OF PITUITARY APOPLEXY MUST BE TAKEN INTO ACCOUNT IN THE DISCUSSION OF SURGICAL VERSUS CONSERVATIVE MANAGEMENT OF NONFUNCTIONING MACROADENOMAS !POPLEXY IS A CLINICAL SYNDROME RESULTING FROM ACUTE HAEMORRHAGE OR INFARCTION OF THE PITUITARY TUMOR )N UNSELECTED PATIENTS WITH .&-!
(239) APOPLEXY IS THE PRESENTING SIGN IN OF THE PATIENTS
(240) /NLY A MINORITY OF PATIENTS PRESENTING WITH APOPLEXY WERE KNOWN TO HARBOUR A PITUITARY TUMOR )N CONTRAST
(241) THE INCIDENCE OF APOPLEXY IN PATIENTS ALREADY KNOWN TO HAVE A PITUITARY TUMOR IS ESTIMATED TO BE LESS THAN YEAR )N PATIENTS WITH MACROADENOMAS THE INCIDENCE OF APOPLEXY IS PROBABLY HIGHER 4HE OCCURRENCE OF PITUITARY APOPLEXY HAS BEEN DESCRIBED FOLLOWING PITUITARY FUNCTION TESTS
(242) CORONARY ARTERY BYPASS SURGERY
(243)
(244) CHOLECYSTECTOMY
(245) HEAD TRAUMA AND VAGINAL DELIVERY -OREOVER
(246) APOPLEXY HAS BEEN ASSOCIATED WITH HYPERTENSION AND ANTICOAGULANT THERAPY 4HE MAJORITY OF PATIENTS WITH PITUITARY APOPLEXY PRESENT WITH !#4( DElCIENCY
(247) ESTABLISHING THE POTENTIAL LIFE THREATENING CONDITION OF THE CLINICAL SYNDROME )N THE PRESENT SERIES PATIENTS PRESENTED WITH PITUITARY APOPLEXY )N OF THESE CASES APOPLEXY WAS ACCOMPANIED BY VISUAL lELD DEFECTS
(248) AND ONE PATIENT HAD MULTIPLE PITUITARY DElCIENCIES $URING FOLLOW UP BOTH THE VISUAL lELD DEFECTS AS WELL AS . .
(249) THE PITUITARY DElCIENCIES RESOLVED WITHIN THREE MONTHS !LTHOUGH THE OPTIMAL TREATMENT FOR .&-! PATIENTS PRESENTING WITH PITUITARY APOPLEXY IS STILL A MATTER OF DEBATE
(250) SURGICAL INTERVENTION IS INDICATED IN PATIENTS PRESENTING WITH TOTAL OR NEAR TOTAL VISUAL LOSS !FTER TRANSSPHENOIDAL SURGERY VISUAL IMPAIRMENT AND OCULAR PARESIS RESOLVES IN THE MAJORITY OF CASES (OWEVER
(251) CONSERVATIVE MANAGEMENT WITH CAREFUL FOLLOW UP
(252) SEEMS APPROPRIATE IN SELECTED PATIENTS WITHOUT
(253) OR WITH ONLY MILD NEURO OPHTALMIC SIGNS
(254) WITHOUT ADVERSELY AFFECTING PATIENT OUTCOMES
(255) )N CONCLUSION
(256) OUR SERIES WITH NON OPERATED .&-! PATIENTS REPORT AN INCREASE IN TU MOR SIZE IN OF ALL PATIENTS DURING LONG TERM FOLLOW UP
(257) ACCOMPANIED BY VISUAL lELD DEFECTS IN OF THESE CASES )N PATIENTS WITH AN INCREASE IN TUMOR SIZE AND VISUAL lELD DEFECTS
(258) SURGICAL TREATMENT RESOLVED THE VISUALS lELD DEFECTS .O INDEPENDENT PREDICTORS FOR TUMOR GROWTH WERE FOUND BY LOGISTIC REGRESSION "ASED ON THESE DATA
(259) WE PROPOSE A CONSERVATIVE APPROACH IN SELECTED PATIENTS WITH .&-! WITHOUT VISUAL lELD DEFECTS )N THESE PATIENTS
(260) THIS IS A SAFE ALTERNATIVE FOR TRANSSPHENOIDAL SURGERY
(261) WITHOUT THE RISK OF . $IBQUFS. IRREVERSIBLY COMPROMISING VISUAL lELD DEFECTS. .
(262) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. 3&'&3&/$&4 &ELDKAMP *
(263) 3ANTEN 2
(264) (ARMS %
(265) !ULICH !
(266) -ODDER 5
(267) 3CHERBAUM 7! )NCIDENTALLY DISCOVERED PITUITARY LESIONS HIGH FREQUENCY OF MACROADENOMAS AND HORMONE SECRETING ADENOMAS n RE SULTS OF A PROSPECTIVE STUDY #LIN%NDOCRINOL/XF -C#OMB $*
(268) 2YAN .
(269) (ORVATH %
(270) +OVACS + 3UBCLINICAL ADENOMAS OF THE HUMAN PITUITARY .EW LIGHT ON OLD PROBLEMS !RCH0ATHOL,AB -ED #OMTOIS 2
(271) "EAUREGARD (
(272) 3OMMA -
(273) 3ERRI /
(274) !RIS *ILWAN .
(275) (ARDY * 4HE CLINICAL AND ENDO CRINE OUTCOME TO TRANS SPHENOIDAL MICROSURGERY OF NONSECRETING PITUITARY ADENOMAS #ANCER -ARAZUELA -
(276) !STIGARRAGA "
(277) 6ICENTE !
(278) %STRADA *
(279) #UERDA #
(280) 'ARCIA 5RIA *
(281) ,UCAS 4 2ECOVERY OF VISUAL AND ENDOCRINE FUNCTION FOLLOWING TRANSSPHENOIDAL SURGERY OF LARGE NONFUNCTIONING PITUITARY ADENOMAS *%NDOCRINOL)NVEST 7ICHERS 2OTHER -
(282) (OVEN 3
(283) +RISTOF 2!
(284) "LIESENER .
(285) 3TOFFEL 7AGNER " .ONFUNCTIONING PITU ITARY ADENOMAS ENDOCRINOLOGICAL AND CLINICAL OUTCOME AFTER TRANSSPHENOIDAL AND TRANSCRANIAL SURGERY %XP#LIN%NDOCRINOL$IABETES 3OTO !RES '
(286) #ORTET 2UDELLI #
(287) !SSAKER 2
(288) "OULINGUEZ !
(289) $UBEST #
(290) $EWAILLY $
(291) 0RUVO *0 -2) PROTOCOL TECHNIQUE IN THE OPTIMAL THERAPEUTIC STRATEGY OF NONFUNCTIONING PITUITARY ADENOMAS %UR*%NDOCRINOL !RAFAH "- 2EVERSIBLE HYPOPITUITARISM IN PATIENTS WITH LARGE NONFUNCTIONING PITUITARY ADENO MAS *#LIN%NDOCRINOL-ETAB 'REENMAN 9
(292) 4ORDJMAN +
(293) +ISCH %
(294) 2AZON .
(295) /UAKNINE '
(296) 3TERN . 2ELATIVE SPARING OF ANTERIOR PITUITARY FUNCTION IN PATIENTS WITH GROWTH HORMONE SECRETING MACROADENOMAS COM PARISON WITH NONFUNCTIONING MACROADENOMAS *#LIN%NDOCRINOL-ETAB .OMIKOS 0
(297) ,ADAR #
(298) &AHLBUSCH 2
(299) "UCHFELDER - )MPACT OF PRIMARY SURGERY ON PITUITARY FUNCTION IN PATIENTS WITH NONFUNCTIONING PITUITARY ADENOMAS n A STUDY ON PATIENTS !CTA .EUROCHIR7IEN 7EBB 3-
(300) 2IGLA -
(301) 7AGNER !
(302) /LIVER "
(303) "ARTUMEUS & 2ECOVERY OF HYPOPITUITARISM AFTER NEU ROSURGICAL TREATMENT OF PITUITARY ADENOMAS *#LIN%NDOCRINOL-ETAB !RAFAH "-
(304) +AILANI 3(
(305) .EKL +%
(306) 'OLD 23
(307) 3ELMAN 72 )MMEDIATE RECOVERY OF PITUITARY FUNC TION AFTER TRANSSPHENOIDAL RESECTION OF PITUITARY MACROADENOMAS *#LIN%NDOCRINOL-ETAB 'REENMAN 9
(308) /UAKNINE '
(309) 6ESHCHEV )
(310) 2EIDER 'ROSWASSER ))
(311) 3EGEV 9
(312) 3TERN . 0OSTOPERA TIVE SURVEILLANCE OF CLINICALLY NONFUNCTIONING PITUITARY MACROADENOMAS MARKERS OF TUMOUR QUIESCENCE AND REGROWTH #LIN%NDOCRINOL/XF $EKKERS /-
(313) 0EREIRA !-
(314) 2OELFSEMA &
(315) 6OORMOLEN *(
(316) .EELIS +*
(317) 3CHROIJEN -!
(318) 3MIT *7
(319) 2OMIJN *! /BSERVATION ALONE AFTER TRANSSPHENOIDAL SURGERY FOR NONFUNCTIONING PITUITARY MAC ROADENOMA *#LIN%NDOCRINOL-ETAB %BERSOLD -*
(320) 1UAST ,-
(321) ,AWS %2
(322) *R
(323) 3CHEITHAUER "
(324) 2ANDALL 26 ,ONG TERM RESULTS IN TRANS SPHENOIDAL REMOVAL OF NONFUNCTIONING PITUITARY ADENOMAS *.EUROSURG 0ARK 0
(325) #HANDLER 7&
(326) "ARKAN !,
(327) /RREGO **
(328) #OWAN *!
(329) 'RIFlTH +!
(330) 4SIEN # 4HE ROLE OF RADIA TION THERAPY AFTER SURGICAL RESECTION OF NONFUNCTIONAL PITUITARY MACROADENOMAS .EUROSURGERY 7OOLLONS !#
(331) (UNN -+
(332) 2AJAPAKSE 92
(333) 4OOMATH 2
(334) (AMILTON $!
(335) #ONAGLEN *6
(336) "ALAKRISH NAN 6 .ONFUNCTIONING PITUITARY ADENOMAS INDICATIONS FOR POSTOPERATIVE RADIOTHERAPY #LIN %NDOCRINOL/XF ,ILLEHEI +/
(337) +IRSCHMAN $,
(338) +LEINSCHMIDT $E-ASTERS "+
(339) 2IDGWAY %# 2EASSESSMENT OF THE ROLE OF RADIATION THERAPY IN THE TREATMENT OF ENDOCRINE INACTIVE PITUITARY MACROADENOMAS .EUROSURGERY . .
(340) $IBQUFS . $ONOVAN ,%
(341) #ORENBLUM " 4HE NATURAL HISTORY OF THE PITUITARY INCIDENTALOMA !RCH)NTERN -ED 2EINCKE -
(342) !LLOLIO "
(343) 3AEGER 7
(344) -ENZEL *
(345) 7INKELMANN 7 4HE @INCIDENTALOMA OF THE PITUITARY GLAND )S NEUROSURGERY REQUIRED *!-! 3ANNO .
(346) /YAMA +
(347) 4AHARA 3
(348) 4ERAMOTO !
(349) +ATO 9 ! SURVEY OF PITUITARY INCIDENTALOMA IN *APAN %UR*%NDOCRINOL !RITA +
(350) 4OMINAGA !
(351) 3UGIYAMA +
(352) %GUCHI +
(353) )IDA +
(354) 3UMIDA -
(355) -IGITA +
(356) +URISU + .ATURAL COURSE OF INCIDENTALLY FOUND NONFUNCTIONING PITUITARY ADENOMA
(357) WITH SPECIAL REFERENCE TO PITUITARY APOPLEXY DURING FOLLOW UP EXAMINATION *.EUROSURG !RAFAH "-
(358) .EKL +%
(359) 'OLD 23
(360) 3ELMAN 72 $YNAMICS OF PROLACTIN SECRETION IN PATIENTS WITH HYPOPITUITARISM AND PITUITARY MACROADENOMAS *#LIN%NDOCRINOL-ETAB 3CHLECHTE *! #LINICAL PRACTICE 0ROLACTINOMA .%NGL*-ED (ARTMAN -,
(361) #ROWE "*
(362) "ILLER "-
(363) (O ++
(364) #LEMMONS $2
(365) #HIPMAN ** 7HICH PATIENTS DO NOT REQUIRE A '( STIMULATION TEST FOR THE DIAGNOSIS OF ADULT '( DElCIENCY *#LIN%NDOCRINOL -ETAB $I #HIRO '
(366) .ELSON +" 4HE VOLUME OF THE SELLA TURCICA !M * 2ADIOL
(367) 0OST +$
(368) -C#ORMICK 0#
(369) "ELLO *! $IFFERENTIAL DIAGNOSIS OF PITUITARY TUMORS %NDOCRINOL -ETAB #LIN.ORTH !M "URROW '.
(370) 7ORTZMAN '
(371) 2EWCASTLE ."
(372) (OLGATE 2#
(373) +OVACS + -ICROADENOMAS OF THE PITUITARY AND ABNORMAL SELLAR TOMOGRAMS IN AN UNSELECTED AUTOPSY SERIES .%NGL*-ED (ALD *+
(374) %LDEVIK /0
(375) 3KALPE )/ #RANIOPHARYNGIOMA IDENTIlCATION BY #4 AND -2 IMAGING AT 4 !CTA 2ADIOL 4SUDA -
(376) 4AKAHASHI 3
(377) (IGANO 3
(378) +URIHARA .
(379) )KEDA (
(380) 3AKAMOTO + #4 AND -2 IMAGING OF CRANIOPHARYNGIOMA %UR2ADIOL #HANSON 0
(381) $AUJAT &
(382) 9OUNG *
(383) "ELLUCCI !
(384) +UJAS -
(385) $OYON $
(386) 3CHAISON ' .ORMAL PITUITARY HYPERTROPHY AS A FREQUENT CAUSE OF PITUITARY INCIDENTALOMA A FOLLOW UP STUDY *#LIN%NDO CRINOL-ETAB #ARDOSO %2
(387) 0ETERSON %7 0ITUITARY APOPLEXY A REVIEW .EUROSURGERY .IELSEN %(
(388) ,INDHOLM *
(389) "JERRE 0
(390) #HRISTIANSEN *3
(391) (AGEN #
(392) *UUL 3
(393) *ORGENSEN *
(394) +RUSE !
(395) ,AU RBERG 0 &REQUENT OCCURRENCE OF PITUITARY APOPLEXY IN PATIENTS WITH NONFUNCTIONING PITUITARY ADENOMA #LIN%NDOCRINOL/XF 3IBAL ,
(396) "ALL 3'
(397) #ONNOLLY 6
(398) *AMES 2!
(399) +ANE 0
(400) +ELLY 7&
(401) +ENDALL 4AYLOR 0
(402) -ATHIAS $
(403) 0ERROS 0
(404) 1UINTON 2
(405) 6AIDYA " 0ITUITARY APOPLEXY A REVIEW OF CLINICAL PRESENTATION
(406) MANAGEMENT AND OUTCOME IN CASES 0ITUITARY -ASAGO !
(407) 5EDA 9
(408) +ANAI (
(409) .AGAI (
(410) 5MEMURA 3 0ITUITARY APOPLEXY AFTER PITUITARY FUNCTION TEST A REPORT OF TWO CASES AND REVIEW OF THE LITERATURE 3URG.EUROL 3AVAGE %"
(411) 'UGINO ,
(412) 3TARR 0!
(413) "LACK 0-
(414) #OHN ,(
(415) !RANKI 3& 0ITUITARY APOPLEXY FOLLOWING CARDIOPULMONARY BYPASS CONSIDERATIONS FOR A STAGED CARDIAC AND NEUROSURGICAL PROCEDURE %UR*#ARDIOTHORAC3URG 9AHAGI .
(416) .ISHIKAWA !
(417) -ATSUI 3
(418) +OMODA 9
(419) 3AI 9
(420) !MAKATA 9 0ITUITARY APOPLEXY FOLLOWING CHOLECYSTECTOMY !NAESTHESIA 5CHIYAMA (
(421) .ISHIZAWA 3
(422) 3ATOH !
(423) 9OKOYAMA 4
(424) 5EMURA + 0OST TRAUMATIC PITUITARY APO PLEXY n TWO CASE REPORTS .EUROL-ED#HIR 4OKYO "IOUSSE 6
(425) .EWMAN .*
(426) /YESIKU .- 0RECIPITATING FACTORS IN PITUITARY APOPLEXY *.EUROL .EUROSURG0SYCHIATRY !YUK *
(427) -C'REGOR %*
(428) -ITCHELL 2$
(429) 'ITTOES .* !CUTE MANAGEMENT OF PITUITARY APOPLEXY n SURGERY OR CONSERVATIVE MANAGEMENT #LIN%NDOCRINOL/XF .
(430) 5IFOBUVSBMDPVSTFPGOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNBTJOOPOPQFSBUFEQBUJFOUT. %LSASSER )MBODEN 0.
(431) $E 4RIBOLET .
(432) ,OBRINUS !
(433) 'AILLARD 2#
(434) 0ORTMANN ,
(435) 0RALONG &
(436) 'OMEZ & !POPLEXY IN PITUITARY MACROADENOMA EIGHT PATIENTS PRESENTING IN MONTHS -EDICINE "ALTIMORE 2ANDEVA (3
(437) 3CHOEBEL *
(438) "YRNE *
(439) %SIRI -
(440) !DAMS #"
(441) 7ASS *! #LASSICAL PITUITARY APOPLEXY CLINICAL FEATURES
(442) MANAGEMENT AND OUTCOME #LIN%NDOCRINOL/XF . .
(443)
(444)
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