Nonfunctioning pituitary macroadenomas : treatment and long-term follow-up
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(2) 1UALITY OF LIFE IS DECREASED IN PATIENTS TREATED FOR NONFUNCTIONING PITUITARY MACROADENOMA. /- $EKKERS
(3) !! VAN DER +LAAUW
(4) !- 0EREIRA
(5) .2 "IERMASZ
(6) 0* (ONKOOP
(7) & 2OELFSEMA
(8) *7! 3MIT
(9) *! 2OMIJN $EPARTMENT OF %NDOCRINOLOGY AND -ETABOLIC $ISEASES
(10) ,EIDEN 5NIVERSITY -EDICAL #ENTER
(11) ,EIDEN
(12) 4HE .ETHERLANDS *OURNAL OF #LINICAL %NDOCRINOLOGY AND -ETABOLISM 3EP . $)"15&3.
(13) 46.."3: /BJECTIVE !LTHOUGH A REDUCED QUALITY OF LIFE 1O, HAS BEEN REPORTED AFTER LONG TERM CURE OF FUNCTIONING PITUITARY ADENOMAS
(14) THE EFFECT OF SUCCESSFUL TREATMENT OF NONFUNCTIONING PITUITARY MACROADENOMA .&-! ON 1O, HAS NOT BEEN FULLY ADDRESSED 4HEREFORE
(15) WE EVALUATED A BROAD SPECTRUM OF 1O, PARAMETERS IN PATIENTS SUCCESSFULLY TREATED FOR .&-! IN OUR CENTER $ESIGN #ASE CONTROL STUDY 0ATIENTS AND -ETHODS 7E ASSESSED 1O, IN ADULT PATIENTS MEAN AGE
(16) RANGE YR
(17) IN REMISSION DURING LONG TERM FOLLOW UP AFTER SURGICAL N AND ADDITIONAL RADIOTHERAPEUTIC N TREATMENT FOR .&-! BY FOUR VALIDATED HEALTH RELATED QUESTION NAIRES (!$3
(18) -&)
(19) .(0
(20) 3& 0ATIENT OUTCOMES WERE COMPARED WITH CONTROLS AND WITH AGE ADJUSTED REFERENCE VALUES DERIVED FROM LITERATURE 2ESULTS .&-! PATIENTS REPORTED SIGNIlCANTLY IMPAIRED 1O, IN ALL QUESTIONNAIRES
(21) COMPARED WITH THE CONTROLS AND THE AGE ADJUSTED REFERENCE VALUES !LL SUBSCALES OF FATIGUE
(22) ASSESSED USING THE MULTI DIMENSIONAL &ATIGUE )NDEX GENERAL FATIGUE
(23) PHYSICAL FATIGUE
(24) REDUCTION IN ACTIVITY
(25) REDUCTION IN MOTIVATION
(26) MENTAL FATIGUE WERE IMPAIRED 4HE $IBQUFS. SCORES IN THE .OTTINGHAM (EALTH 0ROlLE POINTED TOWARDS REDUCED ENERGY AND AFFECTED . . EMOTIONAL REACTION )N SEVERAL SUBSCALES OF THE 3HORT &ORM SOCIAL FUNCTIONING
(27) ROLE LIMITATIONS DUE TO PHYSICAL PROBLEMS
(28) ROLE LIMITATIONS DUE TO EMOTIONAL PROBLEMS AND GENERAL HEALTH PERCEPTION .&-! PATIENTS REPORTED A REDUCED 1O, #ONCLUSION 1UALITY OF ,IFE IS CONSIDERABLY REDUCED IN PATIENTS AFTER SUCCESSFUL TREATMENT OF .&-!.
(29) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. */530%6$5*0/ .ONFUNCTIONING PITUITARY MACROADENOMAS .&-! ARE THE MOST PREVALENT PITUITARY MAC ROADENOMAS 4HE MAIN SYMPTOMS ARE VISUAL lELD DEFECTS AND HYPOPITUITARISM
(30) WHICH ARE CAUSED BY MASS EFFECTS OF THE TUMOR 4RANSSPHENOIDAL SURGERY IS CONSIDERED THE TREATMENT OF CHOICE
(31) BECAUSE MEDICAL THERAPY IN GENERAL IS INEFFECTIVE TO REDUCE TUMOR SIZE 6ISUAL lELD DEFECTS IMPROVE IN MORE THAN OF ALL PATIENTS AFTER SURGERY )N CONTRAST
(32) HYPOPITUITARISM DOES NOT IMPROVE IN MOST PATIENTS AFTER SURGERY FOR .&-! 4O PREVENT TUMOR RECURRENCE
(33) SELECTED PATIENTS MAY BE TREATED BY POSTOPERATIVE RADIOTHERAPY )N GENERAL
(34) PITUITARY DISEASES ARE ASSOCIATED WITH IMPAIRED QUALITY OF LIFE 1O, 4HIS CAN BE EXPLAINED BY SEVERAL FACTORS -ACROADENOMAS ARE ASSOCIATED WITH DIFFER ENT DEGREES OF HYPOPITUITARISM
(35) WHICH REQUIRE HORMONAL SUBSTITUTION (OWEVER
(36) DESPITE OPTIMAL ENDOCRINE REPLACEMENT STRATEGIES
(37) HYPOPITUITARISM IS ASSOCIATED WITH IMPAIRED 1O, PARAMETERS -OREOVER
(38) 'ROWTH HORMONE '( AND !#4( PRODUCING ADENO MAS MAY INDUCE IRREVERSIBLE EFFECTS
(39) WHICH PERSIST DESPITE LONG TERM CURE OF THE DISEASE &INALLY
(40) AN ASSOCIATION BETWEEN APPLIED RADIOTHERAPY AND DECREASED 1O, HAS BEEN REPORTED -OST STUDIES ON 1O, IN PITUITARY DISEASES WERE NOT FOCUSSED ON .&-!
(41) BUT INCLUDED HETEROGENEOUS GROUPS
(42) CONSISTING OF BOTH FUNCTIONING AND NONFUNCTIONING PITUITARY TU MORS 4O OUR KNOWLEDGE
(43) NO STUDIES ON 1O, IN PATIENTS TREATED FOR .&-!
(44) COMPARED WITH HEALTHY CONTROLS
(45) HAVE BEEN PUBLISHED 4HEREFORE
(46) IN THE PRESENT STUDY THE AIM WAS TO ASSESS 1O, IN ADULT .&-! PATIENTS TREATED BY TRANSSPHENOIDAL SURGERY 0ATIENT OUTCOMES OF 1O, PARAMETERS WERE COMPARED WITH THOSE OF CONTROL SUBJECTS AS WELL AS TO AGE ADJUSTED REFERENCE VALUES DERIVED FROM LITERATURE 7E EVALUATED PHYSICAL
(47) PSYCHO LOGICAL
(48) AND SOCIAL ASPECTS OF 1O, IN PATIENTS AFTER LONG TERM CURE
(49) USING FOUR VALIDATED
(50) HEALTH RELATED 1O, QUESTIONNAIRES COVERING A BROAD SPECTRUM OF PHYSICAL
(51) PSYCHOLOGICAL AND SOCIAL HEALTH (!$3
(52) -&)
(53) 3& AND .(0 . 1"5*&/5"/%.&5)0%4. 1SPUPDPM ! TOTAL OF CONSECUTIVE PATIENTS WITH .&-!
(54) TREATED BY TRANSSPHENOIDAL SURGERY IN OUR CENTER BETWEEN AND
(55) WERE IDENTIlED 1O, QUESTIONNAIRES WERE SENT TO THEIR HOMES IN PREPAID ENVELOPES !FTER THREE MONTHS NON RESPONDERS WERE CONTACTED BY TELEPHONE TO ENCOURAGE COMPLETION AND RETURN OF THE QUESTIONNAIRES %ACH PATIENT WAS ALSO ASKED TO PROVIDE A CONTROL PERSON OF COMPARABLE AGE AND SEX TO SERVE AS A CONTROL GROUP WITH A COMPARABLE SOCIO ECONOMIC STATUS DERIVED FROM THE SAME GEOGRAPHICAL . .
(56) AREA )N ADDITION TO THIS CONTROL GROUP
(57) WE USED REFERENCE DATA FROM HEALTHY SUBJECTS OF THE $UTCH AND WEST %UROPEAN POPULATION
(58) OBTAINED FROM STUDIES REPORTING NORMAL AGE ADJUSTED VALUES !LL PATIENTS WERE SEEN AT LEAST TWICE YEARLY BY AN ENDOCRINOLOGIST
(59) WITH ADEQUATE EVALU ATION AND TREATMENT OF POSSIBLE DElCIENCIES OF PITUITARY HORMONES %VALUATION OF !#4( DElCIENCY AND '( DElCIENCY WAS PERFORMED BY INSULIN TOLERANCE TEST 0REVIOUS STUDIES HAVE DEMONSTRATED THAT PATIENTS WITH MULTIPLE PITUITARY HORMONE DElCIENCIES
(60) INCLUDING TWO OR MORE PITUITARY HORMONE DElCIENCIES OTHER THAN '( DElCIENCY
(61) HAD A LIKELIHOOD OF APPROXIMATELY OF HARBOURING '( DElCIENCY "ASED ON THESE DATA
(62) WE CLASSI lED PATIENTS IN WHOM '( STIMULATION TEST DATA WERE LACKING
(63) BUT WHO WERE DElCIENT IN OTHER PITUITARY AXES
(64) AS '( DElCIENT )N ADDITION
(65) THE BIANNUAL EVALUATION CONSISTED OF MEASUREMENT OF FREE 4 AND TESTOSTERONE MALE PATIENTS )F RESULTS WERE BELOW THE LOWER LIMIT OF THE RESPECTIVE REFERENCE RANGES
(66) SUBSTITUTION WITH THYROXINE OR TESTOSTERONE WAS STARTED )N THE CASE OF AMENORRHEA AND LOW ESTRADIOL LEVELS IN PREMENOPAUSAL WOMEN
(67) ESTROGEN REPLACEMENT WAS PROVIDED 4HE MEDICAL ETHICS COMMITTEE OF THE ,EIDEN 5NIVERSITY -EDICAL #ENTRE APPROVED THE . $IBQUFS. STUDY PROTOCOL . . 1BUJFOUTBOEDPOUSPMT 5BCMF. /NE HUNDRED AND SIXTEEN OF PATIENTS RETURNED THE QUESTIONNAIRES
(68) OF WHOM PREFERRED NOT TO PARTICIPATE 4WELVE PATIENTS DID NOT RESPOND 4HUS
(69) COMPLETED QUES TIONNAIRES WERE RECEIVED 4HE STUDY POPULATION HAD A MEAN AGE OF YR
(70) RANGE YR .O SIGNIlCANT DIFFERENCES IN AGE
(71) GENDER AND TUMOR CHARACTERISTICS WERE FOUND BETWEEN THE STUDY POPULATION
(72) AND THE PATIENTS WHO PREFERRED NOT TO PARTICIPATE OR WHO DID NOT RETURN THE QUESTIONNAIRES 3IXTY SIX CONTROLS WERE PROVIDED BY THE PATIENTS WHO RETURNED THE QUESTIONNAIRES 4HE CONTROL GROUP WAS EXTENDED BY CONTROLS DERIVED FROM OTHER STUDIES IN OUR CENTER
(73) WHO HAD BEEN SIMILARLY APPROACHED 4HE TOTAL CONTROL GROUP CONSISTED OF CONTROLS MALES
(74) FEMALES
(75) WITH A MEAN AGE OF YR
(76) RANGE YR !GE AND GENDER FROM THE CONTROL GROUP WERE NOT SIGNIlCANTLY DIFFERENT FROM THE STUDIED .&-! PATIENTS. 4UVEZQBSBNFUFST 0RIMARY STUDY PARAMETERS WERE THE RESULTS OF THE FOUR HEALTH RELATED 1O, QUESTIONNAIRES 4HE RESULTS WERE LINKED TO CHARACTERISTICS AGE AND GENDER OF THE PATIENTS
(77) TREATMENT CHARACTERISTICS SURGERY
(78) RADIOTHERAPY
(79) AND MULTIPLE SURGICAL PROCEDURES
(80) THE PRESENCE OF PITUITARY DElCIENCIES AND VISUAL lELD DEFECTS .
(81) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. 2VFTUJPOOBJSFT (!$3 (OSPITAL !NXIETY AND $EPRESSION 3CALE 4HE (!$3 CONSISTS OF ITEMS PER TAINING TO ANXIETY AND DEPRESSION %ACH ITEM IS MEASURED ON A FOUR POINT SCALE 3CORES FOR THE ANXIETY AND DEPRESSION SUBSCALE RANGE FROM AND FOR THE TOTAL SCORE FROM ! HIGH SCORE POINTS TO MORE SEVERE ANXIETY AND DEPRESSION ! TOTAL SCORE OF OR MORE WAS CONSIDERED INCREASED !GE RELATED $UTCH REFERENCE VALUES OF THE GENERAL POPULATION WERE DERIVED FROM THE STUDY OF 3PINHOVEN ET AL -&) -ULTIDIMENSIONAL &ATIGUE )NDEX 4HE -&) CONTAINS STATEMENTS TO ASSESS FATIGUE &IVE DIFFERENT DIMENSIONS OF FATIGUE FOUR ITEMS EACH ARE CALCULATED FROM THESE STATEMENTS GENERAL FATIGUE
(82) PHYSICAL FATIGUE
(83) REDUCED ACTIVITY
(84) RE DUCED MOTIVATION
(85) AND MENTAL FATIGUE %VERY STATEMENT IS MEASURED ON A POINT SCALE SCORES VARY FROM TO (IGHER SCORES INDICATE HIGHER EXPERIENCED FATIGUE !GE RELATED $UTCH REFERENCE VALUES WERE DERIVED FROM 3METS ET AL .(0 .OTTINGHAM (EALTH 0ROlLE 4HE .(0 IS FREQUENTLY USED IN PATIENTS WITH PITUITARY DISEASE TO ASSESS GENERAL WELL BEING AND 1O, 4HE SURVEY CONSISTS OF YESNO QUESTIONS
(86) WHICH ARE SUBDIVIDED IN SCALES ASSESSING IMPAIRMENTS
(87) IE PAIN ITEMS
(88) ENERGY LEVEL ITEMS
(89) SLEEP ITEMS
(90) EMOTIONAL REACTIONS ITEMS
(91) SOCIAL ISOLATION ITEMS AND DISABILITYFUNCTIONING
(92) IE PHYSICAL MOBILITY ITEMS 3UBSCALE SCORES ARE CALCULATED AS A WEIGHTED MEAN OF THE ASSOCIATED ITEMS AND ARE EXPRESSED AS A VALUE BETWEEN AND 4HE TOTAL SCORE IS THE MEAN OF THE SUBSCALES ! HIGH SCORE IS RELATED TO A WORSE 1O, !GE RELATED 7EST %UROPEAN REFERENCE VALUES WERE DERIVED FROM THE STUDY FROM (INZ ET AL 3& 3HORT &ORM 4HE 3& QUESTIONNAIRE COMPRISES ITEMS AND RECORDS GENERAL WELL BEING DURING THE PREVIOUS DAYS 4HE ITEMS ARE FORMULATED AS STATEMENTS OR QUESTIONS TO ASSESS EIGHT HEALTH CONCEPTS PHYSICAL FUNCTIONING
(93) SOCIAL FUNCTIONING
(94) LIMITATIONS IN USUAL ROLE ACTIVITIES BECAUSE OF PHYSICAL HEALTH PROBLEMS
(95) PAIN
(96) GENERAL MENTAL HEALTH PSYCHOLOGICAL DISTRESS AND WELL BEING
(97) LIMITATIONS IN USUAL ROLE ACTIVITIES BECAUSE OF EMOTIONAL PROBLEMS
(98) VITALITY ENERGY AND FATIGUE
(99) AND GENERAL HEALTH PERCEPTIONS AND CHANGE IN HEALTH "ECAUSE THE (!$3 AND THE -&) ARE MORE SPECIlC QUESTIONNAIRES FOR MENTAL HEALTH AND FATIGUE
(100) THE VITALITY AND GENERAL MENTAL HEALTH ITEMS WERE LEFT OUT IN THIS EVALUATION "ECAUSE THE SCORES FOR THE ITEMS ARE CALCULATED SEPARATELY FROM EXCLUSIVE ITEM SPECIlC QUESTIONS
(101) THE RESULTS OF THE 3& ITEMS PRESENTED IN THIS STUDY ARE NOT INmUENCED BY THE ITEMS WE LEFT OUT IN THIS EVALUATION 3CORES ARE EXPRESSED ON A SCALE (IGHER SCORES ARE ASSOCIATED WITH BETTER 1O, !GE RELATED 7EST %UROPEAN REFERENCE VALUES WERE DERIVED FROM THE $UTCH MANUAL . .
(102) 4UBUJTUJDT 3033 FOR WINDOWS VERSION 3033 )NC
(103) #HICAGO
(104) ), WAS USED FOR DATA ANALYSIS $ATA ARE EXPRESSED AS MEAN ¢ 3$
(105) UNLESS OTHERWISE MENTIONED 7E USED UNPAIRED 4 TESTS TO COMPARE PATIENT AND CONTROL DATA 5SING STEPWISE LINEAR REGRESSION ANALYSIS WE AS SESSED INDEPENDENT VARIABLES THAT AFFECT 1O, 2ESULTS OF THE LINEAR REGRESSION ANALYSIS ARE EXPRESSED AS THE ABSOLUTE STANDARDIZED ` OF INDEPENDENT PREDICTIVE FACTORS /NE WAY !./6! ANALYSIS WAS PERFORMED TO COMPARE 1O, SCORES OF THREE DIFFERENT GROUPS 0ATIENTS WITHOUT '( DElCIENCY
(106) PATIENTS WITH '( DElCIENCY
(107) SUBSTITUTED WITH RECOMBINANT HUMAN RH '( AND PATIENTS WITH '( DElCIENCY WITHOUT RH'H SUBSTITUTION $IFFERENCES WERE CONSIDERED STATISTICALLY SIGNIlCANT AT 0 . 3&46-54. 1BUJFOUBOEUSFBUNFOUDIBSBDUFSJTUJDT 5BCMF. 0ATIENT CHARACTERISTICS ARE DETAILED IN 4ABLE !LL PATIENTS HAD BEEN TREATED BY TRANS SPHENOIDAL SURGERY 4WENTY TWO PATIENTS HAD RECEIVED PROPHYLACTIC POSTOPERATIVE RA $IBQUFS. DIOTHERAPY 2EPEAT SURGERY WITHIN MONTHS AFTER INITIAL TREATMENT WAS PERFORMED IN . . PATIENTS FOR A LARGE RESIDUAL TUMOR MASS N
(108) PERSISTING LIQUOR LEAKAGE N OR PROFUSE BLEEDING N 4HE MEAN FOLLOW UP PERIOD AFTER INITIAL SURGICAL TREATMENT WAS ¢ YR )N PATIENTS TUMOR RECURRENCE WAS OBSERVED BY -2) SCANNING
(109) AFTER A MEAN FOLLOW UP DURATION OF ¢ YR 4UMOR RECURRENCE WAS TREATED BY RADIOTHERAPY N
(110) OR A COMBINATION OF SURGERY AND RADIOTHERAPY N )N THE REMAINING PATIENTS AN EXPECTANT APPROACH WAS UNDERTAKEN !T THE TIME OF EVALUATION
(111) OF THE PATIENTS WERE '( DElCIENT
(112) WERE ,(&3( DE lCIENT
(113) WERE !#4( DElCIENT AND WERE 43( DElCIENT (YPOPITUITARISM
(114) DElNED AS PITUITARY DElCIENCY IN AT LEAST ONE AXIS
(115) WAS PRESENT IN OF PATIENTS
(116) PANHYPOPI TUITARISM OF THE ANTERIOR PITUITARY GLAND IN $IABETES INSIPIDUS WAS PRESENT IN OF THE PATIENTS !LL PATIENTS WITH !#4( AND 43( DElCIENCY RECEIVED HORMONAL SUBSTITUTION THERAPY /F ALL '( DElCIENT PATIENTS
(117) RECEIVED RH'H SUBSTITUTION AT THE TIME OF EVALUATION /F ALL '( DElCIENT PATIENTS WITHOUT SUBSTITUTION AT TIME OF EVALUATION
(118) RH'( WAS STOPPED IN CASES &INALLY
(119) VISUAL lELD DEFECTS WERE PRESENT IN OF CASES . 2VBMJUZPG-JGFJO/'."QBUJFOUTDPNQBSFEXJUIDPOUSPMTBOEBHFBEKVTUFESFGFSFODFWBMVFT 5BCMF .&-! PATIENTS REPORTED AN IMPAIRED 1O, COMPARED WITH THE CONTROLS AND THE AGE ADJUSTED REFERENCE VALUES 4HE 1O, SCORES WERE SIGNIlCANTLY REDUCED IN OUT OF SUBSCALES AS COMPARED WITH OWN CONTROLS
(120) AND IN OUT OF SUBSCALES AS COMPARED WITH AGE ADJUSTED REFERENCE VALUES .
(121) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. 4ABLE #HARACTERISTICS OF .&-! PATIENTS AND CONTROLS. "HF ZS. 4FY .'. "HFBUEJBHOPTJT 1JUVJUBSZGVODUJPO ()EFmDJFODZ .FBO*('*4%TDPSFJOSI()TVCTUJUVUFEQBUJFOUT .FBO*'(*4%TDPSFJO()EFmDJFOU OPOTVCTUJUVUFEQBUJFOUT -)'4)EFmDJFODZ "$5)EFmDJFODZ .FBOEBJMZEPTFPGIZESPDPSUJTPOF NH JOTVCTUJUVUFEQBUJFOUT 54)EFmDJFODZ .FBOGSFF5MFWFMT QNPM- JOTVCTUJUVUFEQBUJFOUT OPSNBM. "OZEFHSFFPGIZQPQJUVJUBSJTN 5XPPSNPSFQJUVJUBSZEFmDJFODJFT 1BOIZQPQJUVJUBSJTNPGUIFBOUFSJPSQJUVJUBSZHMBOE %JBCFUFTJOTJQJEVT (FOFSBMNFEJDBMJMMOFTTBOEEJTBCJMJUZ 7JTVBMmFMEEFGFDUT %JBCFUFT.FMMJUVT $BSEJPWBTDVMBSEJTFBTF +PJOUDPNQMBJOUT. /'."1BUJFOUT / . SBOHF (. $POUSPMT / . SBOHF . . #OMPARED WITH OWN CONTROLS
(122) IN PATIENTS WITH .&-!
(123) ALL SUBSCALES OF THE -&)
(124) AS SESSING DIFFERENT ASPECTS OF ENERGYFATIGUE
(125) WERE AFFECTED 4HE MAJORITY OF ITEMS ASSESSED BY THE 3& AND THE .(0
(126) TWO QUESTIONNAIRES COVERING MULTIPLE ASPECTS OF GENERAL HEALTH AND WELL BEING
(127) WERE AFFECTED WITH THE EXCEPTION OF PAIN .(0 AND 3& AND HEALTH CHANGE 3& /N THE SUBSCALES OF THE (!$3
(128) .&-! PATIENTS PERFORMED WORSE COMPARED WITH OWN CONTROLS #OMPARED WITH AGE ADJUSTED REFERENCE VALUES
(129) THE MAJORITY OF SUBSCALES OF THE -&) WERE AFFECTED
(130) WITH THE EXCEPTION OF GENERAL FATIGUE !CCORDING TO THE 3& SCORES OF OUT OF SUBSCALES WERE REDUCED SOCIAL FUNCTIONING
(131) ROLE LIMITATIONS DUE PHYSICAL
(132) EMO TIONAL PROBLEMS AND GENERAL HEALTH PERCEPTION /NLY TWO SUBSCALES OF THE .(0 ENERGY AND EMOTIONAL REACTION POINTED TOWARD A REDUCED 1O, IN .&-! PATIENTS 4HERE WAS NO SIGNIlCANTLY AFFECTED 1O, PARAMETER ACCORDING TO THE (!$3 QUESTIONNAIRE
(133) COMPARED WITH AGE ADJUSTED REFERENCE VALUES . 5IFFõFDUPG()EFmDJFODZBOE()SFQMBDFNFOUPO2P! SUBSTANTIAL PROPORTION OF THE .&-! PATIENTS WITH '( DElCIENCY WERE NOT SUB STITUTED WITH RH'( 4O ASSESS THE EFFECT OF '( DElCIENCY AND RH'( REPLACEMENT ON 1O,
(134) WE PERFORMED !./6! ANALYSIS COMPARING THREE GROUPS PATIENTS WITHOUT '( DElCIENCY N
(135) PATIENTS WITH '( DElCIENCY
(136) SUBSTITUTED WITH RH'( N AND PATIENTS WITH '( DElCIENCY
(137) BUT WITHOUT RH'H SUBSTITUTION N 4HE ONLY SIGNIlCANT DIFFERENCE BETWEEN . .
(138) 4ABLE 1UALITY OF ,IFE PARAMETERS (!$3
(139) -&)
(140) .(0
(141) 3& IN TREATED .&! PATIENTS COMPARED WITH CONTROLS AND AGE ADJUSTED REFERENCE VALUES. $IBQUFS. )"%4 "OYJFUZ %FQSFTTJPO 5PUBM .'* (FOFSBMGBUJHVF 1IZTJDBMGBUJHVF 3FEVDUJPOJOBDUJWJUZ 3FEVDUJPOJONPUJWBUJPO .FOUBM'BUJHVF /)1 &OFSHZ 1BJO &NPUJPOBMSFBDUJPO 4MFFQ 1IZTJDBMNPCJMJUZ 4PDJBMJTPMBUJPO 4' 1IZTJDBMGVODUJPOJOH 4PDJBMGVODUJPOJOH 3PMFMJNJUBUJPOTEVFUPQIZTJDBMQSPCMFNT 3PMFMJNJUBUJPOTEVFUPFNPUJPOBMQSPCMFNT 1BJO (FOFSBMIFBMUIQFSDFQUJPO )FBMUIDIBOHF. . /'"QBUJFOUT O . $POUSPMT O . QWBMVF. "HFBEKVTUFE SFGFSFODFWBMVFT. QWBMVF. . . . . OT OT OT. . . . . OT . . . OT . . OT OT OT OT. . . OT OT. . OT OT OT. . PATIENTS COMPARED WITH OWN CONTROLS DERIVED FROM REFERENCES PATIENTS COMPARED WITH LITERATURE REFERENCE DATA . THESE THREE GROUPS WAS IN SLEEP PERFORMANCE .(0
(142) 0 3LEEP WAS MOST AFFECTED IN PATIENTS WITH A '( DElCIENCY
(143) SUBSTITUTED WITH RH'( . -JOFBSSFHSFTTJPO 3TEPWISE UNI VARIATE LINEAR REGRESSION ANALYSIS WAS PERFORMED IN A MODEL INCLUDING GEN DER
(144) AGE
(145) RADIOTHERAPY
(146) MULTIPLE OPERATIONS
(147) !#4( DElCIENCY
(148) 43( DElCIENCY
(149) ,(&3( DElCIENCY
(150) '( DElCIENCY
(151) MULTIPLE PITUITARY DElCIENCIES AND VISUAL DEFECTS AS INDEPEN DENT VARIABLES
(152) AND THE QUESTIONNAIRE ITEMS AS DEPENDENT VARIABLES !GE WAS AN INDEPENDENT PREDICTOR FOR REDUCED PHYSICAL ABILITY .(0
(153) STANDARDIZED `
(154) 0 AND REDUCED PHYSICAL FUNCTION 3&
(155) STANDARDIZED `
(156) 0 4HE PRESENCE OF MULTIPLE HORMONAL DElCIENCIES WAS AN INDEPENDENT PREDICTOR FOR ROLE LIMITA TIONS DUE TO PHYSICAL PROBLEMS 3&
(157) STANDARDIZED `
(158) 0
(159) IMPAIRED SOCIAL FUNCTIONING 3&
(160) STANDARDIZED `
(161) 0 AND SLEEP .(0
(162) STANDARDIZED `
(163) 0 AND INCREASED GENERAL FATIGUE -&)
(164) STANDARDIZED `
(165) 0 ,(.
(166) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. &3( DElCIENCY WAS AN INDEPENDENT PREDICTOR FOR REDUCED ACTIVITY -&)
(167) STANDARDIZED `
(168) 0 AND INCREASED PHYSICAL FATIGUE -&)
(169) STANDARDIZED `
(170) 0 &EMALE GENDER WAS AN INDEPENDENT PREDICTOR FOR INCREASED ANXIETY (!$3
(171) STANDARDIZED `
(172) P 2ADIOTHERAPY
(173) VISUAL lELD DEFECTS AND '( DElCIENCY WERE NOT FOUND TO BE INDEPENDENT PREDICTORS FOR REDUCED 1O, IN ANY OF THE QUESTIONNAIRES. %*4$644*0/ 4HE DATA IN THIS STUDY INDICATE THAT QUALITY OF LIFE IS REDUCED IN PATIENTS SUCCESSFULLY TREATED FOR .&-! !CCORDING TO THE PARAMETERS TESTED BY THE (!$3
(174) -&)
(175) .(0 AND 3& QUESTIONNAIRES
(176) PATIENTS REPORTED A DECREASED 1O, IN OUT OF SUBSCALES
(177) COMPARED WITH BOTH AGE ADJUSTED REFERENCE VALUES AND CONTROLS !LMOST ALL SUBSCALES OF THE -&)
(178) ASSESSING ENERGYFATIGUE
(179) SHOWED A SIGNIlCANT DECREASED 1O, ,INEAR REGRESSION ANALYSIS REVEALED THE PRESENCE OF MULTIPLE PITUITARY DElCIENCIES
(180) AND
(181) TO A LESSER EXTENT AGE
(182) AS THE PREDOMINANT PREDICTORS OF A DECREASED 1O, )N THE PRESENT STUDY
(183) .&-! PATIENTS WERE COMPARED WITH OWN CONTROLS AND AGE ADJUST ED REFERENCE VALUES DERIVED FROM LITERATURE 4HE ADVANTAGE OF USING OWN CONTROLS IS THAT THEY ARE FROM THE SAME GEOGRAPHIC AREA AND SOCIO ECONOMIC CLASS AS THE PATIENTS (OWEVER
(184) THESE CONTROLS MIGHT BE SUBJECT TO A SELECTION BIAS
(185) BECAUSE PATIENTS MIGHT HAVE CHOSEN CONTROLS WITH A SUPPOSED GOOD HEALTH STATUS 4O OVERCOME THIS POTENTIAL BIAS
(186) WE ALSO COMPARED THE .&-! PATIENTS TO AGE ADJUSTED REFERENCE VALUES FROM THE LITERATURE -OREOVER
(187) THE USE OF TWO DIFFERENT CONTROL GROUPS MIGHT LEAD TO MORE CREDIBLE RESULTS IF THE RESULTS ARE CONSISTENT 4HE SCORES OF THE .&-! PATIENTS SHOWED AN IMPAIRED 1O, IN MORE SUBSCALES OF THE FOUR QUESTIONNAIRES
(188) COMPARED WITH OWN CONTROLS THAN COMPARED WITH THE AGE ADJUSTED REFERENCE VALUES
(189) CONlRMING THE POSSIBLE DIFFERENCE IN HEALTH STATUS BETWEEN THE TWO GROUPS .ONETHELESS
(190) EVEN COMPARED WITH THE REFERENCE DATA OBTAINED FROM THE LITERATURE
(191) OUR .&-! PATIENTS SCORED WORSE
(192) SUPPORTING OUR CONCLUSIONS WITH RESPECT TO THE NEGATIVE EFFECT OF .&-! ON 1O, !LTHOUGH THE RESPONSE RATE IN OUR SERIES OF PATIENTS WITH .&-! WAS
(193) AND COMPLETED QUESTIONNAIRES WERE RECEIVED OF OF THE PATIENTS
(194) IT SEEMS UNLIKELY
(195) THAT THE NON RESPONDERS HAVE INmUENCED THE OUTCOME OF OUR STUDY
(196) BECAUSE THERE WERE NO DIFFERENCES IN PATIENT CHARACTERISTICS BETWEEN RESPOND ERS AND NON RESPONDERSDECLINERS ,ITERATURE ON 1O, IN PATIENTS WITH .&-! IS SCARCE 4O OUR KNOWLEDGE ONLY TWO STUDIES EVALUATED 1O, IN .&-! PATIENTS *OHNSON ET AL REPORTED A REDUCED 1O, IN .&-! PATIENTS
(197) BEFORE TREATMENT
(198) USING THE 3& QUESTIONNAIRE
(199) COMPARED WITH SCORES FROM THE NORMAL POPULATION /THER REPORTS ON 1O, IN .&-!
(200) CONSISTING OF HETEROGENEOUS GROUPS OF PATIENTS WITH BOTH FUNCTIONING AND NONFUNCTIONING TUMORS
(201) SHOWED A REDUCED 1O, IN PATIENTS WITH PITUITARY TUMORS IN GENERAL (OWEVER
(202) IT WAS NOT POSSIBLE . .
(203) 4ABLE 3UMMARY OF 3& RESULTS IN PATIENTS TREATED FOR NONFUNCTIONING PITUITARY MACROADENOMAS AND IN PATIENTS AFTER MASTOID SURGERY. .FBOBHF ZS. 1IZTJDBMGVODUJPOJOH 1IZTJDBMSPMF &NPUJPOBMSPMF 4PDJBMGVODUJPOJOH #PEJMZQBJO )FBMUIQFSDFQUJPO. /'"USFBUFE PXOEBUB. . .BTUPJETVSHFSZ . . TO PERFORM SUBGROUP ANALYSIS IN ORDER TO ESTIMATE 1O, SPECIlCALLY IN .&-!
(204) BECAUSE OF THE SMALL NUMBER OF PATIENTS -OREOVER
(205) THE EFFECTS OF PITUITARY DISEASES ON 1O, CANNOT SIMPLY BE GENERALIZED FOR ALL PITUITARY DISEASES .&-! PATIENTS DIFFER FROM PATIENTS WITH FUNCTIONING PITUITARY ADENOMAS IN SEVERAL ASPECTS .&-! IS MORE PREVALENT IN OLDER AND MALE PATIENTS COMPARED WITH FUNCTIONING PITUITARY ADENOMAS .ONFUNCTION ING ADENOMAS ARE TREATED ONLY WHEN TUMOR SIZE INDICATES A MACROADENOMA
(206) WHEREAS TREATMENT INDICATION IN FUNCTIONING ADENOMAS IS FOCUSED AT HORMONE OVERPRODUCTION IN $IBQUFS. ADDITION TO TUMOR SIZE 4HEREFORE
(207) PITUITARY TUMORS IN TREATED .&-! TEND TO BE LARGER THAN . . TUMORS IN PATIENTS TREATED FOR FUNCTIONING PITUITARY ADENOMAS )N ACCORDANCE
(208) IN .&-! PATIENTS THERE IS A HIGHER DEGREE OF PITUITARY DElCIENCIES
(209) WHEREAS PATIENTS CURED FROM FUNCTIONING PITUITARY TUMORS ALSO SUFFER FROM IRREVERSIBLE EFFECTS OF PREVIOUS HORMONE OVERPRODUCTION
(210) AS IS THE CASE IN FUNCTIONING ADENOMAS SUCH AS #USHINGS DISEASE OR ACROMEGALY #OMPARED WITH .&-!
(211) 1O, IN ACROMEGALY PATIENTS IS CLEARLY DE CREASED 1O, ASSESSMENT IN HETEROGENEOUS GROUPS
(212) CONSISTING OF BOTH FUNCTIONING AND NONFUNCTIONING ADENOMAS
(213) MAY THEREFORE NOT BE AN APPROPRIATE STRATEGY TO ASSESS 1O, IN PATIENTS TREATED FOR .&-! 4HE STUDY FROM 0AGE ET AL DID NOT REVEAL A REDUCED 1O, IN SURGICALLY TREATED .&-! PATIENTS
(214) COMPARED WITH PATIENTS AFTER MASTOID SURGERY 4HE RESULTS OF THE 3& QUESTIONNAIRE FROM THESE PATIENTS AFTER MASTOID SURGERY ARE SUMMARIZED IN 4ABLE 4HESE RESULTS DO NOT SHOW CONCORDANT DIFFERENCES COMPARED WITH OUR .&-! PATIENTS
(215) POINTING TOWARD A GENERAL ROLE FOR MEDICAL ILLNESS IN IMPAIRED 1O, (OWEVER
(216) THIS ALSO UNDERSCORES THE NOTION THAT THE 3& QUESTIONNAIRE IS NOT DISEASE SPECIlC
(217) IE IS NOT SPECIlC FOR THE ASSESSMENT OF 1O, IN PATIENTS WITH PITUITARY DISEASES /UR RESULTS POINT TOWARD A REDUCED 1O, IN PHYSICAL AND PSYCHOLOGICAL AS WELL SOCIAL ITEMS 4REATED .&-! PATIENTS REPORT INCREASED FATIGUE
(218) BOTH MENTAL AND PHYSICAL
(219) REDUCED ENERGY AND ROLE LIMITATIONS DUE TO PHYSICAL PROBLEMS AS WELL AS REDUCED ACTIVITY AND RE DUCED MOTIVATION )NTERESTINGLY
(220) PHYSICAL FUNCTIONING SEEMED NOT TO BE AFFECTED COMPARED WITH AGE ADJUSTED REFERENCE VALUES .&-! PATIENTS ALSO REPORT AFFECTED EMOTIONAL REAC TIONS
(221) ROLE LIMITATIONS DUE TO EMOTIONAL PROBLEMS AS WELL AS AFFECTED SOCIAL FUNCTIONING .
(222) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. .ONETHELESS
(223) THE (!$3 QUESTIONNAIRE DID NOT REVEAL ANY SIGNIlCANT DIFFERENCE BETWEEN .&-! PATIENTS AND AGE ADJUSTED REFERENCE VALUES 4HIS lNDING IS IN ACCORDANCE WITH THE REPORT OF +ORALI ET AL IN WHICH NO ELEVATED RATES OF MENTAL DISORDERS COULD BE FOUND AFTER TREATMENT FOR .&-!
(224) EVEN IN THE CASE OF MULTIPLE PITUITARY DElCIENCIES 7E COULD NOT PROPERLY ASSESS THE EFFECT OF HYPOPITUITARISM PER SE ON 1O,
(225) BECAUSE HYPOPITUITARISM WAS PRESENT IN OF ALL .&-! PATIENTS !LTHOUGH THE NUMBER OF PA TIENTS WITH HYPOPITUITARISM SEEMS RATHER HIGH
(226) IT IS COMPARABLE TO THE PERCENTAGE OF PATIENTS WITH HYPOPITUITARISM PRESENTED IN A SERIES OF CONSECUTIVE PATIENTS TREATED FOR .&-! IN OUR HOSPITAL 4HE PATIENT POPULATION IN THE PRESENT SERIES SEEMS THEREFORE NOT SKEWED TOWARDS THOSE PATIENTS WITH MORE SEVERE DISEASE (YPOPITUITARISM WAS FOUND TO BE AN INDEPENDENT PREDICTOR OF REDUCED 1O, IN PATIENTS TREATED FOR #USHINGS DISEASE
(227) AFFECTING BOTH PHYSICAL AND PSYCHOSOCIAL ITEMS )N THE PRESENT STUDY
(228) THE PRESENCE OF MULTIPLE PITUITARY DElCIENCIES WAS THE MOST PREDOMINANT PREDICTOR FOR DECREASED 1O,
(229) POINTING TOWARD AN IMPORTANT ROLE OF PITUITARY FUNCTION FOR OPTIMAL 1O, (ORMONAL SUB STITUTION THERAPY DOES NOT REPRODUCE THE NORMAL PLASMA HORMONE PROlLES OF HEALTHY INDIVIDUALS -OREOVER
(230) THE EFFECTS OF HORMONES IN GENERAL ARE DIFlCULT TO QUANTIFY AT THE TISSUE LEVEL #ONSEQUENTLY
(231) TITRATION OF ENDOCRINE REPLACEMENT THERAPY IS POSSIBLE ONLY WITHIN CERTAIN PHYSIOLOGICAL LIMITS 4HESE INTRINSIC IMPERFECTIONS IN ENDOCRINE REPLACE MENT THERAPY MAY RESULT IN SUBTLE PHYSIOLOGICAL DERANGEMENTS -OST IMPORTANTLY
(232) THIS IM PERFECTION IN ENDOCRINE SUBSTITUTION MAY RESULT IN A DECREASED 1O, )N THIS STUDY ,(&3( DElCIENCY WAS AN INDEPENDENT PREDICTOR FOR REDUCED ACTIVITY AND INCREASED PHYSICAL FA TIGUE 4HIS MAY REmECT THE LACK OF SENSITIVE SIGNS AND SYMPTOMS FOR MONITORING ADEQUACY OF TESTOSTERONE AND ESTROGEN SUBSTITUTION 7E DID NOT MEASURE ROUTINELY LEVELS OF DEHYDROEPIANDROSTENEDIONE $(%! (OWEVER
(233) WE RECENTLY DOCUMENTED IN A RANDOM IZED PLACEBO CONTROLLED TRIAL
(234) THAT $(%! SUBSTITUTION SUPERIMPOSED ON '( SUBSTITUTION DID NOT SUBSTANTIALLY IMPROVE 1O, IN PATIENTS WITH SECONDARY ADRENAL FAILURE )N THIS STUDY
(235) FEMALE GENDER WAS AN INDEPENDENT PREDICTOR FOR ANXIETY 4HE PREDISPOSITION FOR FEMALE GENDER AS AN INDEPENDENT RISK FACTOR FOR A DECREASED 1O, IS UNCLEAR
(236) AND HAS BEEN PREVIOUSLY DESCRIBED IN PATIENTS WITH PRIMARY BRAIN TUMORS (OWEVER
(237) IT DOES NOT SEEM TO BE A DISEASE SPECIlC PHENOMENON GIVEN THE FACT THAT 1O, STUDIES IN NONPITUITARY DISEASES MALIGNANCIES
(238) CORONARY HEART DISEASE
(239) INmAMMATORY BOWEL DISEASE ALSO REPORT DECREASED 1O, IN FEMALE PATIENTS AS COMPARED WITH MALE PATIENTS '( DElCIENCY WAS NOT FOUND TO BE AN INDEPENDENT PREDICTOR FOR ANY OF SUBSCALES OF THE FOUR QUESTIONNAIRES )N OUR STUDY ONLY OF ALL '( DElCIENT PATIENTS RECEIVED RH'( SUBSTITUTION 7E COULD NOT DETECT A BENElCIAL EFFECT OF RH'( SUBSTITUTION ON 1O, SCORES (OWEVER
(240) THIS STUDY WAS
(241) IN STRICT SENSE
(242) NOT DESIGNED TO ASSESS THE EFFECT OF RH'( SUBSTITUTION ON 1O, ! RECENT META ANALYSIS ON THE EFFECT OF RH'H SUBSTITUTION ON VARIOUS 1O, SUBSCALES
(243) SUGGESTED THAT RH'( SUBSTITUTION DOES NOT IMPROVE 1O, COMPARED WITH PLACEBO -OREOVER
(244) SEVERAL STUDIES REPORT AN IMPROVED 1O, AND WELL BEING
(245) . .
(246) SUGGESTING THAT IN SELECTED PATIENTS RH'( SUBSTITUTION MAY HAVE A BENElCIAL EFFECT ON 1O, 4HE FOUR HEALTH RELATED QUESTIONNAIRES USED IN THIS STUDY
(247) WERE NOT DISEASE SPECIlC
(248) IE THEY WERE NOT DEVELOPED TO ASSESS 1O, IN .&-!
(249) ALTHOUGH THE .(0 IS FREQUENTLY USED IN PATIENTS WITH PITUITARY DISEASE (OWEVER
(250) WE FOUND A REDUCED 1O, IN THE MAJORITY OF SUB SCALES OF THE -&)
(251) THE 3& AND THE .(0 4HIS SEEMS TO POINT TOWARD A STRONG OVERALL EFFECT OF THE PITUITARY DISEASES ON GENERAL HEALTH AND WELL BEING OF BOTH THE PHYSICAL AND THE PSYCHOSOCIAL ASPECTS )N CONCLUSION
(252) 1UALITY OF ,IFE IS REDUCED IN PATIENTS AFTER SUCCESSFUL TREATMENT OF .&-! !CCORDING TO THE -&)
(253) .(0 AND 3&
(254) PATIENTS REPORTED A DECREASED 1O, IN ALMOST ALL SUBSCALES COMPARED WITH AGE ADJUSTED REFERENCE VALUES AND CONTROLS 4HE PRESENCE OF . $IBQUFS. MULTIPLE PITUITARY DElCIENCIES WAS THE PREDOMINANT PREDICTOR FOR A REDUCED 1O,. .
(255) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. 3&'&3&/$&4 &ELDKAMP *
(256) 3ANTEN 2
(257) (ARMS %
(258) !ULICH !
(259) -ODDER 5
(260) 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 $*
(261) 2YAN .
(262) (ORVATH %
(263) +OVACS + 3UBCLINICAL ADENOMAS OF THE HUMAN PITUITARY .EW LIGHT ON OLD PROBLEMS !RCH 0ATHOL ,AB -ED #OMTOIS 2
(264) "EAUREGARD (
(265) 3OMMA -
(266) 3ERRI /
(267) !RIS *ILWAN .
(268) (ARDY * 4HE CLINICAL AND ENDO CRINE OUTCOME TO TRANS SPHENOIDAL MICROSURGERY OF NONSECRETING PITUITARY ADENOMAS #ANCER %BERSOLD -*
(269) 1UAST ,-
(270) ,AWS %2
(271) *R
(272) 3CHEITHAUER "
(273) 2ANDALL 26 ,ONG TERM RESULTS IN TRANS SPHENOIDAL REMOVAL OF NONFUNCTIONING PITUITARY ADENOMAS * .EUROSURG -ARAZUELA -
(274) !STIGARRAGA "
(275) 6ICENTE ! ET AL 2ECOVERY OF VISUAL AND ENDOCRINE FUNCTION FOLLOWING TRANSSPHENOIDAL SURGERY OF LARGE NONFUNCTIONING PITUITARY ADENOMAS * %NDOCRINOL )NVEST 3CHEITHAUER "7
(276) *AAP !*
(277) (ORVATH % ET AL #LINICALLY SILENT CORTICOTROPH TUMORS OF THE PITUITARY GLAND .EUROSURGERY 'REENMAN 9
(278) 4ORDJMAN +
(279) +ISCH %
(280) 2AZON .
(281) /UAKNINE '
(282) 3TERN . 2ELATIVE SPARING OF ANTERIOR PITUITARY FUNCTION IN PATIENTS WITH GROWTH HORMONE SECRETING MACROADENOMAS COMPARISON WITH NONFUNCTIONING MACROADENOMAS * #LIN %NDOCRINOL -ETAB .OMIKOS 0
(283) ,ADAR #
(284) &AHLBUSCH 2
(285) "UCHFELDER - )MPACT OF PRIMARY SURGERY ON PITUITARY FUNCTION IN PATIENTS WITH NONFUNCTIONING PITUITARY ADENOMAS n A STUDY ON PATIENTS !CTA .EUROCHIR 7IEN 7ICHERS 2OTHER -
(286) (OVEN 3
(287) +RISTOF 2!
(288) "LIESENER .
(289) 3TOFFEL 7AGNER " .ONFUNCTIONING PITU ITARY ADENOMAS ENDOCRINOLOGICAL AND CLINICAL OUTCOME AFTER TRANSSPHENOIDAL AND TRANSCRANIAL SURGERY %XP #LIN %NDOCRINOL $IABETES 0ARK 0
(290) #HANDLER 7&
(291) "ARKAN !, ET AL 4HE ROLE OF RADIATION THERAPY AFTER SURGICAL RESECTION OF NONFUNCTIONAL PITUITARY MACROADENOMAS .EUROSURGERY *OHNSON -$
(292) 7OODBURN #*
(293) 6ANCE -, 1UALITY OF LIFE IN PATIENTS WITH A PITUITARY ADENOMA 0ITUITARY "IERMASZ .2
(294) VAN 4HIEL 37
(295) 0EREIRA !- ET AL $ECREASED QUALITY OF LIFE IN PATIENTS WITH ACROMEGALY DESPITE LONG TERM CURE OF GROWTH HORMONE EXCESS * #LIN %NDOCRINOL -ETAB VAN !KEN -/
(296) 0EREIRA !-
(297) "IERMASZ .2 ET AL 1UALITY OF LIFE IN PATIENTS AFTER LONG TERM BIOCHEMICAL CURE OF #USHINGS DISEASE * #LIN %NDOCRINOL -ETAB 0AGE 2#
(298) (AMMERSLEY -3
(299) "URKE #7
(300) 7ASS *! !N ACCOUNT OF THE QUALITY OF LIFE OF PATIENTS AFTER TREATMENT FOR NONFUNCTIONING PITUITARY TUMOURS #LIN %NDOCRINOL /XF "AIRD !
(301) 3ULLIVAN 4
(302) :AFAR 3
(303) 2OCK * 1UALITY OF LIFE IN PATIENTS WITH PITUITARY TUMORS A PRELIMI NARY STUDY 1UAL -ANAG (EALTH #ARE 0EACE +!
(304) /RME 3-
(305) 4HOMPSON !2
(306) 0ADAYATTY 3
(307) %LLIS !7
(308) "ELCHETZ 0% #OGNITIVE DYSFUNCTION IN PATIENTS TREATED FOR PITUITARY TUMOURS * #LIN %XP .EUROPSYCHOL 4REPP 2
(309) %VERTS 2
(310) 3TETTLER # ET AL !SSESSMENT OF QUALITY OF LIFE IN PATIENTS WITH UNCONTROLLED VS CONTROLLED ACROMEGALY USING THE !CROMEGALY 1UALITY OF ,IFE 1UESTIONNAIRE !CRO1O, #LIN %NDOCRINOL /XF (INZ !
(311) +LAIBERG !
(312) 3CHUMACHER *
(313) "RAHLER % ;4HE PSYCHOMETRIC QUALITY OF THE .OTTINGHAM (EALTH 0ROlLE .(0 IN THE GENERAL POPULATION= 0SYCHOTHER 0SYCHOSOM -ED 0SYCHOL . .
(314) $IBQUFS . 3METS %-
(315) 6ISSER -2
(316) 7ILLEMS 'ROOT !&
(317) 'ARSSEN "
(318) 3CHUSTER 5ITTERHOEVE !,
(319) $E (AES *# &ATIGUE AND RADIOTHERAPY " EXPERIENCE IN PATIENTS MONTHS FOLLOWING TREATMENT "R * #ANCER 3PINHOVEN 0
(320) /RMEL *
(321) 3LOEKERS 00
(322) +EMPEN ')
(323) 3PECKENS !%
(324) VAN (EMERT !- ! VALIDATION STUDY OF THE (OSPITAL !NXIETY AND $EPRESSION 3CALE (!$3 IN DIFFERENT GROUPS OF $UTCH SUBJECTS 0SYCHOL -ED 6AN DER :EE +)
(325) 3ANDERMAN 2 (ET METEN VAN DE ALGEMENE GEZONDHEIDSTOESTAND MET DE 2!.$
(326) EEN HANDLEIDING .OORDELIJK #ENTRUM VOOR 'EZONDHEIDSVRAAGSTUKKEN
(327) 'RONINGEN
(328) 4HE .ETHERLANDS 6ANDER:EE +)
(329) 3ANDERMAN 2
(330) (EYINK * ! COMPARISON OF TWO MULTIDIMENSIONAL MEASURES OF HEALTH STATUS THE .OTTINGHAM (EALTH 0ROlLE AND THE 2!.$ )TEM (EALTH 3URVEY 1UAL ,IFE 2ES "ATES !3
(331) %VANS !*
(332) *ONES 0
(333) #LAYTON 2. !SSESSMENT OF '( STATUS IN ADULTS WITH '( DEl CIENCY USING SERUM GROWTH HORMONE
(334) SERUM INSULIN LIKE GROWTH FACTOR ) AND URINARY GROWTH HORMONE EXCRETION #LIN %NDOCRINOL /XF (ARTMAN -,
(335) #ROWE "*
(336) "ILLER "-
(337) (O ++
(338) #LEMMONS $2
(339) #HIPMAN ** 7HICH PATIENTS DO NOT REQUIRE A '( STIMULATION TEST FOR THE DIAGNOSIS OF ADULT '( DElCIENCY * #LIN %NDOCRINOL -ETAB 4OOGOOD !!
(340) "EARDWELL #'
(341) 3HALET 3- 4HE SEVERITY OF GROWTH HORMONE DElCIENCY IN ADULTS WITH PITUITARY DISEASE IS RELATED TO THE DEGREE OF HYPOPITUITARISM #LIN %NDOCRINOL /XF :IGMOND !3
(342) 3NAITH 20 4HE HOSPITAL ANXIETY AND DEPRESSION SCALE !CTA 0SYCHIATR 3CAND 3METS %-
(343) 'ARSSEN "
(344) "ONKE "
(345) $E (AES *# 4HE -ULTIDIMENSIONAL &ATIGUE )NVENTORY -&) PSYCHOMETRIC QUALITIES OF AN INSTRUMENT TO ASSESS FATIGUE * 0SYCHOSOM 2ES (UNT 3-
(346) -C+ENNA 30
(347) -C%WEN *
(348) "ACKETT %-
(349) 7ILLIAMS *
(350) 0APP % ! QUANTITATIVE APPROACH TO PERCEIVED HEALTH STATUS A VALIDATION STUDY * %PIDEMIOL #OMMUNITY (EALTH (UNT 3-
(351) -C%WEN * 4HE DEVELOPMENT OF A SUBJECTIVE HEALTH INDICATOR 3OCIOL (EALTH )LLN "RAZIER *%
(352) (ARPER 2
(353) *ONES .- ET AL 6ALIDATING THE 3& HEALTH SURVEY QUESTIONNAIRE NEW OUTCOME MEASURE FOR PRIMARY CARE "-* 7ARE *%
(354) *R
(355) 3HERBOURNE #$ 4HE -/3 ITEM SHORT FORM HEALTH SURVEY 3& ) #ONCEP TUAL FRAMEWORK AND ITEM SELECTION -ED #ARE 'RIMES $!
(356) 3CHULZ +& #OMPARED WITH WHAT &INDING CONTROLS FOR CASE CONTROL STUDIES ,ANCET 7ACHOLDER 3
(357) 3ILVERMAN $4
(358) -C,AUGHLIN *+
(359) -ANDEL *3 3ELECTION OF CONTROLS IN CASE CONTROL STUDIES )) 4YPES OF CONTROLS !M * %PIDEMIOL 0EACE +!
(360) /RME 3-
(361) 3EBASTIAN *0 ET AL 4HE EFFECT OF TREATMENT VARIABLES ON MOOD AND SOCIAL ADJUSTMENT IN ADULT PATIENTS WITH PITUITARY DISEASE #LIN %NDOCRINOL /XF 0EACE +!
(362) /RME 3-
(363) 0ADAYATTY 3*
(364) 'ODFREY (0
(365) "ELCHETZ 0% #OGNITIVE DYSFUNCTION IN PATIENTS WITH PITUITARY TUMOUR WHO HAVE BEEN TREATED WITH TRANSFRONTAL OR TRANSSPHENOIDAL SURGERY OR MEDICATION #LIN %NDOCRINOL /XF -INDERMANN 4
(366) 7ILSON #" !GE RELATED AND GENDER RELATED OCCURRENCE OF PITUITARY ADENOMAS #LIN %NDOCRINOL /XF +ORALI :
(367) 7ITTCHEN (5
(368) 0lSTER (
(369) (OmER -
(370) /EFELEIN 7
(371) 3TALLA '+ !RE PATIENTS WITH PITUITARY ADENOMAS AT AN INCREASED RISK OF MENTAL DISORDERS !CTA 0SYCHIATR 3CAND .
(372) 2VBMJUZPGMJGFJTEFDSFBTFEJOQBUJFOUTUSFBUFEGPSOPOGVODUJPOJOHQJUVJUBSZNBDSPBEFOPNB. $EKKERS /-
(373) 0EREIRA !-
(374) 2OELFSEMA & ET AL /BSERVATION ALONE AFTER TRANSSPHENOIDAL SURGERY FOR NONFUNCTIONING PITUITARY MACROADENOMA * #LIN %NDOCRINOL -ETAB 2OMIJN *!
(375) 3MIT *7
(376) ,AMBERTS 37 )NTRINSIC IMPERFECTIONS OF ENDOCRINE REPLACEMENT THERAPY %UR * %NDOCRINOL VAN 4HIEL 37
(377) 2OMIJN *!
(378) 0EREIRA !- ET AL %FFECTS OF DEHYDROEPIANDROSTENEDIONE
(379) SUPERIM POSED ON GROWTH HORMONE SUBSTITUTION
(380) ON QUALITY OF LIFE AND INSULIN LIKE GROWTH FACTOR ) IN PATIENTS WITH SECONDARY ADRENAL INSUFlCIENCY A RANDOMIZED
(381) PLACEBO CONTROLLED
(382) CROSS OVER TRIAL * #LIN %NDOCRINOL -ETAB -AINIO !
(383) (AKKO (
(384) .IEMELA !
(385) +OIVUKANGAS *
(386) 2ASANEN 0 'ENDER DIFFERENCE IN RELATION TO DEPRESSION AND QUALITY OF LIFE AMONG PATIENTS WITH A PRIMARY BRAIN TUMOR %UR 0SYCHIATRY !GEWALL 3
(387) "ERGLUND -
(388) (ENAREH , 2EDUCED QUALITY OF LIFE AFTER MYOCARDIAL INFARCTION IN WOMEN COMPARED WITH MEN #LIN #ARDIOL "ERNKLEV 4
(389) *AHNSEN *
(390) !ADLAND % ET AL (EALTH RELATED QUALITY OF LIFE IN PATIENTS WITH INmAM MATORY BOWEL DISEASE lVE YR AFTER THE INITIAL DIAGNOSIS 3CAND * 'ASTROENTEROL -YSTAKIDOU +
(391) 4SILIKA %
(392) 0ARPA %
(393) +ATSOUDA %
(394) 'ALANOS !
(395) 6LAHOS , !SSESSMENT OF !NXIETY AND $EPRESSION IN !DVANCED #ANCER 0ATIENTS AND THEIR 2ELATIONSHIP WITH 1UALITY OF ,IFE 1UAL ,IFE 2ES .ORRIS #-
(396) 'HALI 7!
(397) 'ALBRAITH 0$
(398) 'RAHAM --
(399) *ENSEN ,!
(400) +NUDTSON -, 7OMEN WITH CORONARY ARTERY DISEASE REPORT WORSE HEALTH RELATED QUALITY OF LIFE OUTCOMES COMPARED WITH MEN (EALTH 1UAL ,IFE /UTCOMES !RWERT ,)
(401) $EIJEN *"
(402) 7ITLOX *
(403) $RENT -, 4HE INmUENCE OF GROWTH HORMONE '( SUBSTITUTION ON PATIENT REPORTED OUTCOMES AND COGNITIVE FUNCTIONS IN '( DElCIENT PATIENTS A META ANALY SIS 'ROWTH (ORM )'& 2ES "LUM 7&
(404) 3HAVRIKOVA %0
(405) %DWARDS $* ET AL $ECREASED QUALITY OF LIFE IN ADULT PATIENTS WITH GROWTH HORMONE DElCIENCY COMPARED WITH GENERAL POPULATIONS USING THE NEW
(406) VALIDATED
(407) SELF WEIGHTED QUESTIONNAIRE
(408) QUESTIONS ON LIFE SATISFACTION HYPOPITUITARISM MODULE * #LIN %NDOCRINOL -ETAB $EIJEN *"
(409) !RWERT ,)
(410) 7ITLOX *
(411) $RENT -, $IFFERENTIAL EFFECT SIZES OF GROWTH HORMONE REPLACE MENT ON 1UALITY OF ,IFE
(412) WELL BEING AND HEALTH STATUS IN GROWTH HORMONE DElCIENT PATIENTS A META ANALYSIS (EALTH 1UAL ,IFE /UTCOMES 'IBNEY *
(413) 7ALLACE *$
(414) 3PINKS 4 ET AL 4HE EFFECTS OF YR OF RECOMBINANT HUMAN GROWTH HOR MONE '( IN ADULT '( DElCIENT PATIENTS * #LIN %NDOCRINOL -ETAB 3TOUTHART 0*
(415) $EIJEN *"
(416) 2OFFEL -
(417) $ELEMARRE VAN DE 7AAL (! 1UALITY OF LIFE OF GROWTH HORMONE '( DElCIENT YOUNG ADULTS DURING DISCONTINUATION AND RESTART OF '( THERAPY 0SYCHONEUROENDOCRINOLOGY 3ONKSEN 0(
(418) -C'AULEY ' ,IES
(419) DAMN LIES AND STATISTICS 'ROWTH (ORM )'& 2ES . .
(420)
(421)
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