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The Journal of Clinical Endocrinology & Metabolism 90(6):3337–3341
Copyright © 2005 by The Endocrine Society
doi: 10.1210/jc.2004-1565
Quality of Life (QOL) in Patients with Acromegaly Is
Severely Impaired: Use of a Novel Measure of QOL:
Acromegaly Quality of Life Questionnaire
Susannah V. Rowles, L. Prieto, X. Badia, Steven M. Shalet, Susan M. Webb, and Peter J. Trainer
Department of Endocrinology (S.V.R., S.M.S., P.J.T.), Christie Hospital, Manchester M20 4BX, United Kingdom; Hospital
Sant Pau (S.M.W.), Autonomous University of Barcelona, E-08025 Barcelona, Spain; Spanish Group for the Study of
Methodology in Clinical Research (L.P.), 28108 Madrid, Spain; and Health Outcomes Research Europe Group (X.B.), 08201
Barcelona, Spain
Acromegaly Quality of Life Questionnaire (AcroQoL) is a new disease-generated quality of life (QOL) questionnaire comprising 22
questions covering physical and psychological aspects of acromegaly and subdivided into “appearance” and “personal relations” categories. We have performed a cross-sectional study of QOL in 80
patients [43 male (mean age, 54.2 yr; range, 20 – 84); median GH,
0.93ng/ml (range, ⬍0.3 to 23.7); IGF-I, 333.1 ng/ml (range, 47.7–
899)] with acromegaly. In addition to AcroQoL, patients completed
three generic QOL questionnaires: Psychological General WellBeing Schedule (PGWBS), EuroQol, and a signs and symptoms
score (SSS). All three generic questionnaires confirmed impairment in QOL [mean scores: PGWBS, 69.6; EuroQol, visual analog
A
DVANCES IN SURGICAL technique, modalities of
radiotherapy, and availability of potent medical
therapy mean that we are entering an era when it will be
possible to achieve biochemical disease control in virtually
all patients with acromegaly and thereby restore life expectancy to normal (1–5). The challenge in the future will
be developing treatment algorithms for individual patients that use the various modes of treatment in an optimal manner not only to establish biochemical control but
also to achieve the other goals of therapy, such as controlling tumor growth, protecting vision, reversing soft
tissue changes, preventing arthritis, and preserving pituitary function while ensuring the best possible quality of
life (QOL) for the patient. The means of measuring biochemical markers have improved, but there is a lack of
specific QOL measurement tools for patients with acromegaly and, as a consequence, a dearth of data relating
QOL to biochemical parameters and modalities of treatment. Signs and symptoms scores (SSS) have been used as
measures of efficacy in therapeutic intervention studies
and, unsurprisingly, have been shown to improve as GH
and IGF-I fall (6, 7). However, SSS have not been shown
First Published Online March 8, 2005
Abbreviations: AcroQoL, Acromegaly Quality of Life Questionnaire;
GHD, GH deficiency; PGWB, Psychological General Well-Being;
PGWBS, PGWB Schedule; QOL, quality of life; SSS, signs and symptoms
score(s); UI, utility index(s); VAS, visual analog scale.
JCEM is published monthly by The Endocrine Society (http://www.
endo-society.org), the foremost professional society serving the endocrine community.
scale, 66.4 (range, 20 –100) and utility index, 0.7 (range, ⫺0.07 to
0.92); and SSS, 12 (range, 0 –27)]. There was no correlation between
biochemical control and any measure of QOL. AcroQoL (57.3%;
range, 18.2–93.2) correlated with PGWBS (r ⫽ 0.73; P ⬍ 0.0001);
and in patients with active disease, AcroQoL-physical dimension
correlated with SSS (r ⫽ ⫺0.67; P ⬍ 0.0003). In all questionnaires,
prior radiotherapy was associated with impaired QOL. In conclusion, these data underline the marked impact that acromegaly has
on patients’ QOL and provide the first evidence validating AcroQoL
against well-authenticated measures of QOL. This indicates the
potential of AcroQoL as a patient-friendly measure of disease
activity. (J Clin Endocrinol Metab 90: 3337–3341, 2005)
to relate, in cross-sectional studies, to biochemical measures of disease control and are not measures of QOL but
rather are specifically designed to assess the reversible
consequences of GH hypersecretion, such as perception of
soft tissue swelling and sweating.
The Acromegaly Quality of Life Questionnaire (AcroQoL) was designed with the aim of creating a simple and
valid instrument to assess QOL in people with acromegaly
(8). It is intended to provide a cost-effective means to
assess self-perceived status and to allow evaluation of
interventions, in longitudinal research, and to identify
patients who require further treatment. It was developed
by semistructured, in-depth interviews of patients and
endocrinologists to identify perceived domains of impact
of acromegaly on QOL. Domains identified were: physical
and psychological function, social and daily activities,
symptoms, cognition, general health perception, sleep,
sexual function, pain, energy, and body image. The items
fall into two categories of physical and psychological function, the latter category being subdivided into areas addressing appearance and personal relationships. These
data were pared down to 22 questions with five possible
responses scoring 1–5 (maximum score, 110). Results are
quoted as a percentage, with lower scores equating to
poorer QOL. Originally developed in Spanish, AcroQoL
has been translated into 12 languages (9).
The intention of this study was to assess the QOL of patients with acromegaly using well-authenticated generic
measures of QOL and, for the first time in English patients,
AcroQoL.
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J Clin Endocrinol Metab, June 2005, 90(6):3337–3341
Patients and Methods
Patients
Eighty English-speaking patients [43 male; mean age, 54.2 yr (range,
20 – 84)] with acromegaly, attending for routine care at Christie Hospital,
participated in this study (Table 1).
Ethical permission was obtained from the ethical review board; and
informed, written consent was obtained from the patients. The questionnaires were completed during routine out-patient clinic attendances.
Questionnaires
Patients completed four questionnaires.
The Psychological General Well-Being (PGWB) Index. The PGWB Index is
a 22-item questionnaire addressing both positive and negative affective
states. Each item has six questions, answered on a scale of 0 –5; the
maximum score is 110, reflecting perfect QOL. The items divide into six
subscales: anxiety, depressed mood, positive well-being, self-control,
general health, and vitality. This questionnaire has been shown to have
good validity, reliability, and internal consistency (10).
The SSS. The SSS is a disease-specific tool that consists of five questions,
scoring 0 – 8, considering headache, perspiration, joint pain, fatigue, and
soft tissue swelling. The maximum score of 40 is indicative of severe
signs and symptoms.
AcroQoL. AcroQoL comprises 22 questions, each having five possible
responses scored 1–5, the maximum score of 110 reflecting best possible
QOL, and quoted as a percentage. The 22 items break down into
two categories, physical and psychological function, the latter being
further subdivided into areas addressing appearance and personal
relationships.
EuroQol (EQ-5D). EQ-5D was designed specifically to complement other
QOL instruments and generate a cardinal index of health (11–13). Described as a non-disease-specific tool, it has been well validated, and
normative data exist. Divided into two parts, comprising a five-point
TABLE 1. Age, interval since diagnosis, and modes of therapy of
the 80 patients with acromegaly
Variable
Total no. patients
Age
Sex
Years from diagnosis
Previous treatment of acromegaly
Surgery alone
Radiotherapy alone
Surgery ⫹ radiotherapy
Neither
Current treatment of acromegaly
Dopamine agonist alone
Somatostatin analogue alone
Pegvisomant alone
Combination of two agents
Treatment of hypopituitarism
No replacement therapy
T4 alone
Hydrocortisone alone
Hydrocortisone ⫹ T4
T4 ⫹ sex steroid
Hydrocortisone ⫹ sex steroid
Sex steroid alone
Hydrocortisone ⫹ T4 ⫹ sex steroid
GH/IGF-I axis status
Median GH
Median IGF-I
Value
80
Mean, 54.2 yr
(range, 20 – 84)
43 male
Mean, 9.5
(range, ⬍1 to 30)
10 (12.5%)
11 (13.8%)
43 (53.8%)
16 (20%)
15 (18%)
20 (25%)
6 (7.5%)
4 (5%)
31 (38%)
2 (3%)
12 (15%)
7 (9%)
3 (4%)
5 (6%)
10 (12.5%)
10 (12.5%)
0.93 ng/ml
(range, ⬎1 to 71.2)
333.1 ng/ml
(range, 47.1– 899)
Rowles et al. • QOL in Acromegalics
CRS (category rating scale) addressing mobility/self-care/usual activities/pain and discomfort/anxiety and depression. One response from
three options is selected for each of the five points. Two hundred fortythree permutations are possible, and the utility index (UI) is calculated
using a regression equation (range, ⫺0.59 to 0.92). Part 2 is a self-rated
visual analog scale (VAS), a 20-cm thermometer scaled 0 (worst imaginable health state) to 100 (best imaginable health state).
Assays
Serum IGF-1 and GH were measured using the Nichols Advantage
Method (Nichols Institute Diagnostics, Heston, Middlesex, UK), with an
IGF-I intraassay CV of 7.4, 5.7, and 4.5% at 49, 229, and 493 ␮g/liter,
respectively, and a GH intraassay CV of 7, 8.7, and 8.6% at 2.8, 7.0, and
13.3 ng/ml, respectively. GH was originally measured in milliunits per
liter, and a conversion factor of 3 was used to convert to nanograms per
milliliter.
Statistics
Statistical analysis was with SPSS/S Plus software packages. Linear
regression was used to investigate the relationships between normally
distributed parameters, and Spearman rank order correlation for nonparametric data. Statistical significance was set at the 5% level (P ⬍ 0.05).
Results
The median GH and IGF-I values were 0.93 ng/ml (range,
⬍0.3 to 23.7) and 333.1 ng/ml (range, 47.7– 899), respectively,
with 27 of the 80 patients having an IGF-I within the agerelated reference range and a GH level less than 1.6 ng/ml.
The median scores for the generic, non-disease-specific measures of QOL were: for PGWB, a score of 69.6 (range, 21–104),
with the subsets for vitality and general health having the
greatest deficit (see Fig. 3 and Table 2); and for EuroQol, a
VAS value of 66.4 (range, 20 –100) and UI of 0.7 (range, ⫺0.07
to 0.92). The median score for the disease-generated QOL tool
AcroQoL was 57.3% (range, 18.2–93.2), whereas median SSS
was 12 (range, 0 –27). No difference was found in QOL between those patients with an IGF-I within the age- and sexmatched reference range plus a GH less than 1.6 ng/ml, and
those with biochemically active disease. All patients either
had received treatment for acromegaly in the past or were
currently on medication at the time of questionnaire
completion.
The validity of AcroQoL as a measure of QOL was reinforced by correlations with the non-disease-specific tools:
PGWB Schedule (PGWBS) (r ⫽ 0.73; P ⬍ 0.0001; Fig. 1),
EuroQol VAS (r ⫽ 0.61; P ⬍ 0.001; Fig. 2), UI (r ⫽ 0.63; P ⬍
0.001). The AcroQoL “physical” subcategory correlated with
the SSS (r ⫽ ⫺0.67; P ⬍ 0.0003).
In all questionnaires, stepwise linear regression identified
a history of prior radiotherapy to be associated with worse
TABLE 2. Comparison of PGWB total and subdomain scores in
patients with acromegaly to population-raised normative data
Anxiety
Depression
Well-being
Self-control
General health
Vitality
Total
a
P ⫽ 0.05.
Acromegaly
General population
16.98
11.31
10.96
11.71
8.37
9.61
69.6
17.89
12.36
13.15
13.00
12.21a
13.57a
82.18a
Rowles et al. • QOL in Acromegalics
FIG. 1. AcroQoL scores in patients with acromegaly correlate with
the generic measure of QOL PGWBS (r ⫽ 0.73; P ⬍ 0.0001)
QOL (P ⬍ 0.05). The diagnosis of acromegaly had been made
a mean of 12.7 yr (range, 0.6 –30) previously in the radiotherapy cohort of patients, as opposed to a mean of 7 yr
(range, ⬍1 to 19.4) (P ⬍ 0.0006) in the remainder. No correlation existed between QOL and gender, age at diagnosis,
years from diagnosis, or presence of hypopituitarism.
Discussion
The recent series of consensus publications on the goals of
treatment of acromegaly have concentrated on relating mortality to biochemical parameters to set targets of therapy (14).
Mortality, GH, and IGF-I have the virtues of being easily
measurable; but to patients, well-being is paramount, although more difficult to quantify. Advances in treatment
options mean that it may be possible to achieve biochemical
control in virtually all patients; and therefore, the challenge
is to achieve that goal while ensuring optimal QOL for the
individual patient (7). Many factors influence QOL, and it
may be that the various modes of therapy impact on QOL
differently. Recognition of the improvement in well-being
with GH treatment is responsible for much of the momentum
driving replacement therapy in patients with GH deficiency
(GHD) (15). Many generic tools for measuring QOL have
been used in adults with GHD; but because of its ease of
FIG. 2. AcroQoL scores in patients with acromegaly correlate with
the generic measure of QOL EQ-5 VAS (EQ-VAS) (r ⫽ 0.61; P ⬍
0.0001)
J Clin Endocrinol Metab, June 2005, 90(6):3337–3341
3339
completion, the disease-generated tool Adult GH Deficiency
Assessment has been widely adopted (16 –19). Arising from
an appreciation of the need to measure QOL in patients with
acromegaly, AcroQoL was developed as a series of questions
reflecting topics highlighted during structured interviews
with patients and endocrinologists, and piloted in Spanish
patients (9). This is the first study to report on the use of
AcroQoL in English-speaking patients and to compare its
performance against generic measures of QOL. Further validation of the English translation and general applicability of
AcroQol is that the mean score in the Spanish patients (59.5%;
range, 13.6 –90.9) is very similar to the score in the patients
reported here (57.3%; range, 18.2–93.2).
Confirmation of the severe impairment of QOL in acromegaly comes from comparison between the PGWB scores
from our patients with normative data from population surveys, with the subdomain scores for vitality and general
health being most impaired (20 –22) (Table 2). Consistent
with these findings was the impaired EQ-5D UI score of 0.7,
compared with the population-based mean of 0.81 (23).
These generic measures of QOL allow comparison of the
QOL of patients with acromegaly to that of patients with
other chronic disease. In our patients, the EQ-5D VAS score
was 0.66, compared with 0.79 in asthmatics, 0.69 in angina,
and 0.6 in patients with osteoarthritis (23, 24). A measure of
the severity of the impairment of QOL of patients with acromegaly is that the mean PGWB score in our patients is
worse than in any published series of adults with GHD,
except that reported by Murray et al. (25), who specifically
selected their cohort based on severely impaired QOL at
interview (Fig. 3).
As a disease-generated measure of QOL, no populationderived control data are available for AcroQoL, but the close
correlations demonstrated between AcroQoL scores and
those of the generic tools PGWB and EQ-5D reinforce the
concept that AcroQoL is a valid measure of disease activity,
with the advantages of being focused on the areas of concern
for patients with acromegaly and being patient friendly.
SSS focus on the most reversible aspects of acromegaly
and, for that reason, have been used in many interventional
studies; but their limited focus means that they are not measures of QOL. Furthermore, whereas therapy studies show
an improvement in SSS that coincides with a reduction in GH
and IGF-I, the changes in SSS do not correlate with the
changes in GH and IGF-I. In other words, it is not the patients
with the greatest biochemical improvement that experience
the greatest improvement in SSS. For these reasons, SSS are
of very limited value as measures of well-being in patients
with acromegaly, either in a cross-sectional or longitudinal
study.
This study was cross-sectional in design, with acromegaly
having been diagnosed, on average, 12.7 yr earlier. A wide
spectrum of disease activity existed among the patient cohort, although the median GH and IGF-I levels were 0.93
ng/ml and 333.1 ng/ml, respectively, i.e. virtually within the
biochemical goals for therapy set out in the consensus statement on the treatment of acromegaly (14). A total of 34.2%
of the patients had both GH and IGF-I levels within target;
but despite this degree of biochemical control, measured
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J Clin Endocrinol Metab, June 2005, 90(6):3337–3341
Rowles et al. • QOL in Acromegalics
FIG. 3. PGWBS scores from community surveys and studies of patients with adult GHD, patients following therapy
for nonfunctioning pituitary adenomas and acromegaly (redrawn from Ref. 17).
QOL was significantly impaired with all generic well-being
tools.
No relationship existed between either GH or IGF-I and
any measure of QOL, and there was no difference in QOL
score between those with active and inactive disease. The
absence of a relationship between biochemical parameters
and QOL should not be a surprise. Despite extensive investigation over the last decade of QOL in adults with GHD, and
impairment of QOL being an indication for GH treatment,
there have been no reports of a relationship between either
GH or IGF-I levels and QOL at baseline, or during treatment
of patients with GHD. The potential for observing a relationship between biochemical parameters and QOL in our
patients with acromegaly is diminished by the relatively
satisfactory GH and IGF-I levels. Many factors, other than
circulating levels of GH and IGF-I, are likely to impact on
QOL. In this study, stepwise forward linear regression identified previous radiotherapy as being associated with a significant worsening of QOL; but no effect of gender, age, years
from diagnosis, or presence of hypopituitarism was seen. The
relationship between prior radiotherapy and impairment of
QOL in patients with acromegaly requires further exploration and does not prove radiotherapy to be the cause of
impaired QOL because, for example, the patients treated
with radiotherapy were diagnosed, on average, 11 yr previously, compared with 4 yr for those not treated with radiotherapy, and referral patterns for radiotherapy have
evolved in the last decade. Interestingly, Page et al. (20) found
the PGWB scores to be lower in patients with hypopituitarism who had received radiotherapy, compared with those
who had not. In both studies, it is probable that it was the
patients with larger and more aggressive tumors that were
treated with radiotherapy.
In summary, all measures of QOL have been demonstrated
to be significantly impaired in this cohort of patients with
acromegaly, and to be worse than most adults with severe
GHD. The close correlation of total score and the subsection
for vitality with robust generic QOL tools confirms the validity of AcroQoL as a measure of disease activity. At this
juncture, it would be premature to conclude that radiotherapy is responsible for impairing QOL in patients with acromegaly, and further studies are required to assess the causal
factors. Prospective studies are on-going to see whether favorable changes in biochemical disease activity are reflected
in improvement in AcroQoL score. The long-term goal of
measurement of QOL is to allow selection of the modes of
therapy that not only ensure biochemical control but also
optimize QOL.
Acknowledgments
We express our gratitude to Margaret Roberts (Research Nurse) for
her diligence in overseeing the completion of the questionnaires and to
David Ryder for statistical assistance.
Received August 5, 2004. Accepted February 25, 2005.
Address all correspondence and requests for reprints to: Peter J.
Trainer, Department of Endocrinology, Christie Hospital, Wilmslow
Road, Manchester M20 4BX, United Kingdom. E-mail: peter.trainer@
man.ac.uk.
References
1. Trainer PJ 2002 A giant’s step forward. Clin Endocrinol (Oxf) 56:423– 425
2. Beauregard C, Truong U, Hardy J, Serri O 2003 Long-term outcome and
mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol (Oxf) 58:86 –91
3. Holdaway IM, Rajasoorya RC, Gamble GD 2004 Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89:667– 674
4. Serri O, Beauregard C, Hardy J 2004 Long-term biochemical status and disease-related morbidity in 53 postoperative patients with acromegaly. J Clin
Endocrinol Metab 89:658 – 661
5. Swearingen B, Barker FG, Katznelson L, Biller BM, Grinspoon S, Klibanski
A, Moayeri N, Black PM, Zervas NT 1998 Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol
Metab 83:3419 –3426
6. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der
Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM,
Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL,
Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G,
Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ 2000
Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342:1171–1177
7. van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson
L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart
PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips
LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO
2001 Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358:1754 –1759
8. Badia X, Webb SM, Prieto L, Lara N 2004 Acromegaly Quality of Life Questionnaire (AcroQoL). Health Qual Life Outcomes 2:13
9. Webb SM, Prieto L, Badia X, Albareda M, Catala M, Gaztambide S, Lucas
T, Paramo C, Pico A, Lucas A, Halperin I, Obiols G, Astorga R 2002 Acromegaly Quality of Life Questionnaire (AcroQol) a new health-related quality
Rowles et al. • QOL in Acromegalics
10.
11.
12.
13.
14.
15.
16.
17.
18.
of life questionnaire for patients with acromegaly: development and psychometric properties. Clin Endocrinol (Oxf) 57:251–258
Dupuy HJ 1984 The Psychological General Well-Being (PGWB) Index. In:
Wenger NK, ed. Assessment of quality of life in clinical trials of cardiovascular
therapies. New York: Le Jacq Publishing Inc.; 170 –183
Dolan P 1997 Modeling valuations for EuroQol health states. Med Care 35:
1095–1108
Badia X, Herdman M, Schiaffino A 1999 Determining correspondence between scores on the EQ-5D “thermometer” and a 5-point categorical rating
scale. Med Care 37:671– 677
Brooks R 1996 EuroQol: the current state of play. Health Policy 37:53–72
Giustina A, Barkan A, Casanueva FF, Cavagnini F, Frohman L, Ho K,
Veldhuis J, Wass J, von Werder K, Melmed S 2000 Criteria for cure of
acromegaly: a consensus statement. J Clin Endocrinol Metab 85:526 –529
Holmes SJ, Shalet SM 1995 Characteristics of adults who wish to enter a trial
of growth hormone replacement. Clin Endocrinol (Oxf) 42:613– 618
McKenna SP, Doward LC, Alonso J, Kohlmann T, Niero M, Prieto L, Wiren
L 1999 The QoL-AGHDA: an instrument for the assessment of quality of life
in adults with growth hormone deficiency. Qual Life Res 8:373–383
Murray RD, Skillicorn CJ, Howell SJ, Lissett CA, Rahim A, Shalet SM 1999
Dose titration and patient selection increases the efficacy of GH replacement
in severely GH deficient adults. Clin Endocrinol (Oxf) 50:749 –757
Murray RD, Shalet SM 1999 The use of self-rating questionnaires as a quan-
J Clin Endocrinol Metab, June 2005, 90(6):3337–3341
19.
20.
21.
22.
23.
24.
25.
3341
titative measure of quality of life in adult growth hormone deficiency. J Endocrinol Invest 22(5 Suppl):118 –126
Monson JP 2000 Application of a disease-specific, quality-of-life measure
(QoL-AGHDA) in growth hormone-deficient adults and a random population
sample in Sweden: validation of the measure by Rasch analysis. Clin Endocrinol (Oxf) 52:141–142
Page RC, Hammersley MS, Burke CW, Wass JA 1997 An account of the quality
of life of patients after treatment for non-functioning pituitary tumours. Clin
Endocrinol (Oxf) 46:401– 406
Andersson P, Olaison G, Bendtsen P, Myrelid P, Sjodahl R 2003 Health
related quality of life in Crohn’s proctocolitis does not differ from a general
population when in remission. Colorectal Dis 5:56 – 62
McGauley GA, Cuneo RC, Salomon F, Sonksen PH 1990 Psychological wellbeing before and after growth hormone treatment in adults with growth
hormone deficiency. Horm Res 33(Suppl 4):52–54
Burstrom K, Johannesson M, Diderichsen F 2001 Swedish population healthrelated quality of life results using the EQ-5D. Qual Life Res 10:621– 635
Brazier JE, Harper R, Munro J, Walters SJ, Snaith ML 1999 Generic and
condition-specific outcome measures for people with osteoarthritis of the knee.
Rheumatology (Oxford) 38:870 – 877
Murray RD, Skillicorn CJ, Howell SJ, Lissett CA, Rahim A, Smethurst LE,
Shalet SM 1999 Influence on quality of life in GH deficient adults and their
effect on response to treatment. Clin Endocrinol (Oxf) 51:565–573
JCEM is published monthly by The Endocrine Society (http://www.endo-society.org), the foremost professional society serving the
endocrine community.