***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The insulin tolerance test ( ITT ) is considered the test of choice for the diagnosis of GH deficiency ( GHD ) . However , in patients with contraindications to ITT , alternative provocative tests must be used with appropriate cut-offs . The glucagon stimulation test has proved to be a safe , low-cost and effective means of stimulating GH secretion , and therefore can be considered as a suitable alternative to the ITT . We have studied the GH response to the glucagon test in 33 patients with known pituitary disease , 12 males and 21 females , aged between 21 and 60 yr ( 41.18±9.47 yr ) ; 5 had isolated GHD and 28 had panhypopituitarism . We also evaluated a control group of 25 individuals , matched for age and sex ( 8 males and 17 females ) , aged between 20 and 60 yr ( 39.28±12.10 yr ) . They were selected via the ITT if their peak GH response was > 5.0 ng/ml . GH peak after glucagon was significantly lower in the group of patients compared to the control group ( 0.49±0.85 vs 8.69±5.85 ng/ml , p=0.0001 ) . Receiver-operating characteristic ( ROC ) plot analyses of the control and GHD group showed an area under the curve of 0.982 for GH peak response to glucagon . The response value of 3.0 ng/ml showed the best pair of sensitivity (97%)/specificity ( 88 % ) , and was chosen as the cut-off defining GHD . After evaluation of positive predictive values ( PPV ) and negative predictive values ( NPV ) through simulation of different prevalences of the disease , we concluded that the cut-off point of 3.00 ng/ml maximizes both PPV and NPV ( 100 % ) . In conclusion , we have shown that the glucagon stimulation test has a good performance and great diagnostic accuracy for the diagnosis of GHD OBJECTIVE The glucagon stimulation test ( GST ) like the insulin tolerance test ( ITT ) stimulates both ACTH and GH secretion . However , there are limited data with modern assays on sensitivity and specificity for GST in comparison to ITT . The aim of this study was to evaluate the diagnostic utility of the GST for GH deficiency ( GHD ) and adrenal insufficiency ( AI ) in patients following pituitary surgery . DESIGN AND PATIENTS ITT and GST were performed within 7 days in 49 patients at least 3 months after transsphenoidal surgery .  Serum GH and cortisol were measured by Immulite 2000 assay ( Siemens AG ) . Receiver-operating characteristic ( ROC ) analysis was performed to identify the thresholds for GST . RESULTS In ITT , 18/49 cases were classified as AI . ROC analysis revealed a peak cortisol value > 599 nmol/l in GST for adrenal sufficiency with 100 % specificity and 32 % sensitivity , and a peak cortisol < 277 nmol/l with > 95 % specificity and 72 % sensitivity for AI . Of the 49 subjects , 25 ( 51 % ) demonstrated levels between these cut-offs and could not be diagnosed by GST alone with sufficient accuracy . Regarding GHD , 21/49 cases were classified as insufficient by ITT . ROC analysis revealed a cut-off of 2.5 ng/ml with 95 % sensitivity and 79 % specificity . Of the 49 cases , seven ( 14 % ) were discordant in terms of defining GHD , with six subjects being treated for GHD according to GST although being sufficient in ITT . CONCLUSION In our prospect i ve series of patients with pituitary disease , GST is a potential alternative test for the assessment of GH reserve , but is a poor test for ACTH reserve . Test-specific cut-offs should be applied to avoid misinterpretation objective Reduction of plasma free fatty acids leads to enhanced GH response after stimulation by GH‐releasing hormone ( GHRH ) . We studied the clinical usefulness of combined administration of acipimox and GHRH for the diagnosis of GH deficiency In the attempt to define a GH stimulation test with high specificity and reproductibility , few studies have addressed the influence of potential interfering external factors on the test result . We therefore tested the influence of physical activity ( admission to hospital on test morning ) and mild heat exposure on the GH response to l‐arginine stimulation test ( Arg ) and insulin‐tolerance test  (  ITT ) BACKGROUND AND OBJECTIVE Publication bias and other sample size effects are issues for meta-analyses of test accuracy , as for r and omized trials . We investigate limitations of st and ard funnel plots and tests when applied to meta-analyses of test accuracy and look for improved methods . METHODS Type I and type II error rates for existing and alternative tests of sample size effects were estimated and compared in simulated meta-analyses of test accuracy . RESULTS Type I error rates for the Begg , Egger , and Macaskill tests are inflated for typical diagnostic odds ratios ( DOR ) , when disease prevalence differs from 50 % and when thresholds favor sensitivity over specificity or vice versa . Regression and correlation tests based on functions of effective sample size are valid , if occasionally conservative , tests for sample size effects . Empirical evidence suggests that they have adequate power to be useful tests . When DORs are heterogeneous , however , all tests of funnel plot asymmetry have low power . CONCLUSION Existing tests that use st and ard errors of odds ratios are likely to be seriously misleading if applied to meta-analyses of test accuracy . The effective sample size funnel plot and associated regression test of asymmetry should be used to detect publication bias and other sample size related effects BACKGROUND Adult growth hormone ( GH ) deficiency must be diagnosed before prescribing therapeutic recombinant human GH . We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency ( GHD ) using IGF-1 determination as a first step . METHODS In 2000 and 2001 , we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test ( ITT ) , the reference test for the diagnosis of GHD , with concomitant Insulin-like growth factor-1 ( IGF-1 ) determination , a marker of somatotropic function . Patients were classified as GHD ( peak GH concentration<3 ng/ml with the ITT ) or normal . SETTING Monocenter prospect i ve study in a tertiary referral center . RESULTS  GHD was diagnosed in 61 subjects . Using a ROC curve , a threshold IGF-1 concentration of 175 ng/ml yielded a negative predictive value of 89+/-5 % . A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients , avoided 46/142 ITT and reduced the cost of diagnosis by 15 % . CONCLUSION We propose the use of a strategy consisting of IGF-1 determination followed , if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults Although the use of the insulin tolerance test ( ITT ) for the diagnosis of adult GH deficiency is well established , diagnostic peak GH cut-points for other commonly used GH stimulation tests are less clearly established . Despite that fact , the majority of patients in the United States who are evaluated for GH deficiency do not undergo insulin tolerance testing . The aim of this study was to evaluate the relative utility of six different methods of testing for adult GH deficiency currently used in practice in the United States and to develop diagnostic cut-points for each of these tests . Thirty-nine patients ( 26 male , 13 female ) with adult-onset hypothalamic-pituitary disease and multiple pituitary hormone deficiencies were studied in comparison with age- , sex- , estrogen status- , and body mass index-matched control subjects ( n = 34 ; 20 male , 14 female ) . A third group of patients ( n = 21 ) with adult-onset hypothalamic-pituitary disease and no more than one additional pituitary hormone deficiency was also studied . The primary end-point was peak serum GH response to five GH stimulation tests administered in r and om order at five separate visits : ITT , arginine ( ARG ) , levodopa ( L-DOPA ) , ARG plus L-DOPA , and ARG plus GHRH . Serum IGF-I concentrations were also measured on two occasions . For purpose s of analysis , patients with multiple pituitary hormone deficiencies were assumed to be GH deficient . Three diagnostic cut-points were calculated for each test to provide optimal separation of multiple pituitary hormone deficient and control subjects according to three criteria : 1 ) to minimize misclassification of control subjects and deficient patients ( balance between high sensitivity and high specificity ) ; 2 ) to provide 95 % sensitivity for GH deficiency ; and 3 ) to provide 95 % specificity for GH deficiency . The greatest diagnostic accuracy occurred with the ITT and the ARG plus GHRH test , although patients preferred the latter ( P = 0.001 ) . Using peak serum GH cut-points of 5.1 microg/liter for the ITT and 4.1 microg/liter for the ARG plus GHRH test , high sensitivity ( 96 and 95 % , respectively ) and specificity ( 92 and 91 % , respectively ) for GH deficiency were achieved . To obtain 95 % specificity , the peak serum GH cut-points were lower at 3.3 microg/liter and 1.5 microg/liter for the ITT and ARG plus GHRH test , respectively . There was substantial overlap between patients and control subjects for the ARG plus L-DOPA , ARG , and L-DOPA tests , but test-specific cut-points could be defined for all three tests to provide 95 % sensitivity for GH deficiency ( peak GH cut-points : 1.5 , 1.4 and 0.64 microg/liter , respectively ) . However , 95 % specificity could be achieved with the ARG plus L-DOPA and ARG tests only with very low peak GH cut-points ( 0.25 and 0.21 microg/liter , respectively ) and not at all with the L-DOPA test . Although serum IGF-I levels provided less diagnostic discrimination than all five GH stimulation tests , a value below 77.2 microg/liter was 95 % specific for GH deficiency . In conclusion , the diagnosis of adult GH deficiency can be made without performing an ITT , provided that test-specific cut-points are used . The ARG plus GHRH test represents an excellent alternative to the ITT for the diagnosis of GH deficiency in adults This is the second in a series of five articles Considerable effort has been expended at the interface between clinical medicine and scientific methods to achieve the maximum validity and usefulness of diagnostic tests . This article focuses on the specific kinds of questions that arise in diagnostic research and the study architectures ( the conversions of these clinical questions into appropriate research design s ) used to answer them . As an example we shall take shall take assessment of the value of the plasma concentration of B-type natriuretic peptide ( BNP )  in the diagnosis of left ventricular dysfunction.1  R and omised controlled trials are dealt with elsewhere . As in other forms of clinical research , there are several different ways study ing the potential or real diagnostic value of a physical sign or laboratory test , and each is appropriate to one kind of question and inappropriate for others . Among the possible questions about the relation between a putative diagnostic test and a target disorder ( for example , the concentration of BNP and left ventricular dysfunction ) , four are most relevant . # # # # Summary points Diagnostic studies should match methods to diagnostic questions The keys to validity in diagnostic test studies are Both specificity and sensitivity may change as the same diagnostic test is applied in primary , 
    Output:
    
Serum levels of GH or IGF1 had low diagnostic accuracy .
Several tests with reasonable diagnostic accuracy are available for the diagnosis of GHD in adults .