scholarly journals Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD

2016 ◽  
Vol 175 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Chiara Guzzetti ◽  
Anastasia Ibba ◽  
Sabrina Pilia ◽  
Nadia Beltrami ◽  
Natascia Di Iorgi ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Children And Adolescents ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Igf I ◽  
Stimulation Tests

ObjectiveThe diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents.DesignRetrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests.MethodsSeventy four patients with organic GHD (GH peak <10μg/L after two provocative tests) and 298 control subjects (GH response >10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS.ResultsThe optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity.ConclusionsThe results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

scholarly journals Update on the diagnosis of GH deficiency in adults

2003 ◽  
pp. S3-S8 ◽  
Author(s):  
R Abs
Keyword(s):  
Gh Deficiency ◽  
Tolerance Test ◽  
Cranial Irradiation ◽  
Pituitary Hormone ◽  
Childhood Onset ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Stimulation Tests ◽  
History Of ◽  
Considerable Morbidity

GH deficiency (GHD) in adults is associated with considerable morbidity and mortality. The diagnosis of GHD is generally straightforward in children as growth retardation is present; however, in adults, diagnosis of GHD is often challenging. Other markers are therefore needed to identify adults who have GHD and could potentially benefit from GH replacement therapy. Consensus guidelines for the diagnosis and treatment of adult GHD recommend provocative testing of GH secretion for patients who have evidence of hypothalamic-pituitary disease, patients with childhood-onset GHD, and patients who have undergone cranial irradiation or have a history of head trauma. Suspicion of GHD is also heightened in the presence of other pituitary hormone deficits. Tests for GHD include measurement of the hormone in urine or serum or measurement of stimulated GH levels after administration of various provocative agents. The results of several studies indicate that non-stimulated serum or urine measurements of GH levels cannot reliably predict deficiency in adults. Although glucagon and arginine tests produce a pronounced GH response with few false positives, the insulin tolerance test (ITT) is currently considered to be the gold standard of the GH stimulation tests available. Unfortunately, the ITT has some disadvantages and questionable reproducibility, which have prompted the development of several new tests for GHD that are based on pharmacological stimuli. Of these, GH-releasing hormone (GHRH) plus arginine and GHRH plus GH-releasing peptide (GHRP) appear to be reliable and practical. Thus, in cases where ITT is contraindicated or inconclusive, the combination of arginine and GHRH is an effective alternative. As experience with this test as well as with GHRH/GHRP-6 accumulates, they may supplant ITT as the diagnostic test of choice.

scholarly journals Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests

2021 ◽  
Vol 12 ◽  
Author(s):  
Fabio Bioletto ◽  
Mirko Parasiliti-Caprino ◽  
Alessandro Maria Berton ◽  
Nunzia Prencipe ◽  
Valeria Cambria ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Quantitative Estimation ◽  
Tolerance Test ◽  
Stimulation Test ◽  
Internal Validation ◽  
Risk Class ◽  
Insulin Tolerance ◽  
Adult Gh Deficiency ◽  
Igf I ◽  
Stimulation Tests

BackgroundThe diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results.MethodsEighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests.ResultsAn independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (&lt;25%) pre-test GHD probability could be predicted when IGF-I SDS &gt; +0.91 in the presence of other pituitary deficits or IGF-I SDS &gt; -0.52 in the absence of other pituitary deficits. A high (&gt;75%) pre-test GHD probability could be predicted when IGF-I SDS &lt; -0.82 in the presence of other pituitary deficits or IGF-I SDS &lt; -2.26 in the absence of other pituitary deficits.ConclusionThis is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis.

scholarly journals Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement

2005 ◽  
Vol 152 (4) ◽  
pp. 589-596 ◽  
Author(s):  
Mohamad Maghnie ◽  
Gianluca Aimaretti ◽  
Simonetta Bellone ◽  
Gianni Bona ◽  
Jaele Bellone ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Diagnostic Accuracy ◽  
Normative Data ◽  
Transition Period ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Integrated Analysis ◽  
Insulin Tolerance ◽  
Igf I

Objective: A consensus exists that severe growth hormone deficiency (GHD) in adults is defined by a peak GH response to insulin-induced hypoglycemia (insulin tolerance test, ITT) of less than 3 μg/l based on a cohort of subjects with a mean age of 45 years. Design and methods: By considering one of the following two criteria for the diagnosis of probable permanent GHD, i.e. the severity of GHD (suggested by the presence of multiple pituitary hormone deficiencies (MPHD)) or the magnetic resonance (MR) imaging identification of structural hypothalamic–pituitary abnormalities, 26 patients (17 males, 9 females, mean age 20.8±2.3 years, range 17–25 years) were selected for re-evaluation of the GH response to ITT and their IGF-I concentration. Eight subjects had isolated GHD (IGHD) and 18 had MPHD. Normative data for peak GH were obtained after ITT in 39 healthy subjects (mean age 21.2±4.4 years, range 15.1–30.0 years) and the reference range for IGF-I was calculated using normative data from 117 healthy individuals. Results: Mean peak GH response to ITT was significantly lower in the 26 patients (1.8±2.0 μg/l, range 0.1–6.1 μg/l) compared with the 39 controls (18.5±15.5 μg/l, range 6.1–84.0 μg/l; P < 0.0001). One subject with septo-optic dysplasia had a peak GH response of 6.1 μg/l that overlapped the lowest peak GH response obtained in normal subjects. There was an overlap for IGF-I SDS between subjects with IGHD and MPHD, as well as with normal controls. The diagnostic accuracy of a peak GH response of 6.1 μg/l showed a 96% sensitivity with 100% specificity. The maximum diagnostic accuracy with IGF-I SDS was obtained with a cut-off of −1.7 SDS (sensitivity 77%, specificity 100%) while an IGF-I ≤ − 2.0 SDS showed a sensitivity of 62%. Conclusion: Our data show that the cut-off value of the peak GH response to ITT of less than 3 μg/l or 5 μg/l and of IGF-I of less than −2.0 SDS are too restrictive for the diagnosis of permanent GH deficiency in the transition period. We suggest that permanent GHD could be investigated more accurately by means of an integrated analysis of clinical history, the presence of MPHD, IGF-I concentration and the MR imaging findings of structural hypothalamic–pituitary abnormalities.

scholarly journals Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly

2006 ◽  
Vol 154 (5) ◽  
pp. 659-666 ◽  
Author(s):  
S Pekic ◽  
M Doknic ◽  
D Miljic ◽  
M Joksimovic ◽  
J Glodic ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Provocation Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Provocative Test ◽  
Gh Secretion ◽  
Control Subjects ◽  
Igf I ◽  
Secretory Capacity ◽  
Igfbp 3

Objective: Posttreatment assessment of disease activity and definition of cure of acromegaly, using measurement of GH secretion, remains problematic. Furthermore, with our efforts to achieve tight biochemical control of the disease it is foreseeable that a proportion of patients may be rendered GH deficient, thus requiring testing for GH deficiency. The aim of our study was to evaluate residual GH secretion in cured patients with acromegaly. Design and methods: At baseline, circulating GH, IGF-I, IGFBP-3, leptin and lipid (cholesterol and tri-glycerides) levels were measured in 33 acromegalic patients nine years after treatment with surgery of whom 6 were additionally irradiated. Two tests were performed: the GH suppression test - oral glucose tolerance test (OGTT) and the GH provocation test - ghrelin test (1 μg/kg i.v. bolus) and the results were compared with 11 age- and sex-matched control subjects. Results: According to the consensus criteria (normal IGF-I levels and post-OGTT GH nadir <1 μg/l), 21 treated acromegalic patients were cured, 6 had discordant IGF-I and GH nadir values during OGTT, while 6 had persistent acromegaly. After the GH provocative test with ghrelin (cut-off for severe GH deficiency is GH <3 μg/l), we detected 9 severely GH deficient patients (GHD) among 21 cured acromegalic patients. Mean GH peak (±s.e.m.) response to the ghrelin test in GHD acromegalics was significantly lower compared with acromegalics with sufficient GH secretory capacity and control subjects (1.2 ± 0.2 μg/l vs 20.1 ± 2.4 μg/l vs 31.1 ± 2.5 μg/l respectively, P<0.0001). Mean IGF-I and IGFBP-3 levels were not different between GHD and GH-sufficient cured acromegalics. Leptin levels and body mass index (BMI) were significantly higher in GHD male acromegalics compared with GH-sufficient male acromegalics. GHD female acromegalics tended to have higher BMIs while leptin levels were not different. Conclusions: The assessment of residual GH secretory capacity by the GH provocation test is necessary in the long-term follow-up of successfully treated acromegalics since a large proportion of these patients are rendered GH deficient.

scholarly journals Influence of Body Mass Index and Gender on Growth Hormone (GH) Responses to GH-Releasing Hormone Plus Arginine and Insulin Tolerance Tests

2005 ◽  
Vol 90 (3) ◽  
pp. 1563-1569 ◽  
Author(s):  
Xiao-Dan Qu ◽  
Irene T. Gaw Gonzalo ◽  
Mohammed Y. Al Sayed ◽  
Pejman Cohan ◽  
Peter D. Christenson ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Gender Differences ◽  
Body Mass ◽  
Healthy Subjects ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Insulin Tolerance ◽  
Stimulation Tests ◽  
And Gender

The aim of this study is to assess whether gender and body mass index (BMI) should be considered in developing thresholds to define GH deficiency, using GH responses to GHRH + arginine (ARG) stimulation and insulin tolerance test (ITT). Thirty-nine healthy subjects (19 males, 20 females; ages 21–50 yr) underwent GHRH + ARG, and another 27 subjects (19 males, 8 females; ages 20–49 yr) underwent ITT. Peak GH response was significantly higher (P = 0.005) after GHRH + ARG than with ITT, and this difference could not be explained by age, gender, or BMI. Peak GH response was negatively correlated with BMI in both tests (GHRH + ARG, r = −0.76; and ITT, r = −0.65). Peak GH response to GHRH + ARG was higher in females than males (P = 0.004; ratio = 2.4), but it was attenuated after eliminating the influence of BMI (P = 0.13; ratio = 1.6). No significant gender differences were found in peak GH responses to ITT, which could be due to the smaller number of female subjects studied. GH response to GHRH + ARG and ITT stimulation is sensitive to BMI differences and less so to gender differences. A higher BMI is associated with a depressed GH response to both stimulation tests. BMI should therefore be considered as a factor when defining the diagnostic cut-off points in the assessment of GH deficiency, whereas whether gender should be likewise used is inconclusive from this study.

scholarly journals Diagnostic utility of the glucagon stimulation test in comparison to the insulin tolerance test in patients following pituitary surgery

2010 ◽  
Vol 162 (3) ◽  
pp. 477-482 ◽  
Author(s):  
Christian Berg ◽  
Timo Meinel ◽  
Harald Lahner ◽  
Ali Yuece ◽  
Klaus Mann ◽  
...  
Keyword(s):  
Roc Analysis ◽  
Pituitary Surgery ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Stimulation Test ◽  
Diagnostic Utility ◽  
Glucagon Stimulation Test ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Potential Alternative

ObjectiveThe 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 patientsITT 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.ResultsIn 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.ConclusionIn our prospective 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.

scholarly journals Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test

2002 ◽  
pp. 667-672 ◽  
Author(s):  
S Petersenn ◽  
R Jung ◽  
FU Beil
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Group Versus ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Hormone Deficiency ◽  
Peak Response ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Ghrh Test

OBJECTIVE: The diagnosis of GH deficiency in adults should be made using provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard investigation. Because of the risk of serious complications, patients with epilepsy or known ischemic heart disease should not undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding to specific hypothalamic and pituitary receptors. We assessed the diagnostic capability of GH stimulation by GHRP-6 alone or in combination with GHRH in comparison to the results of an ITT. DESIGN: Twenty patients underwent an ITT for suspected pituitary or adrenal disease. Either GHRP-6 (1 microg/kg) alone, or GHRP-6 in combination with GHRH (1 microg/kg) were administered on different days. Blood samples were obtained during a subsequent 90-min period for measurement of GH. RESULTS: Ten patients had a GH peak response of less than 3 microg/l during ITT and were considered growth hormone deficient (GHD). The GH mean peak (+/-S.E.M., range) in this group was 0.7 microg/l (+/-0.3, 0.1-2.9) compared with 14.5 microg/l (+/-3.5, 3.8-40.8) in the group of patients with a GH peak response of more than 3 microg/l (growth hormone sufficient (GS)). For the GHRP-6 test, the GH mean peak was 1.3 microg/l (+/-0.6, 0.1-6.7) in the GHD group versus 25.7 microg/l (+/-5.5, 7.7-54.2) in the GS group. After GHRP-6+GHRH, the GH mean peaks were 4.0 microg/l (+/-1.3, 0.2-11.9) versus 54.7 microg/l (+/-11.1, 13.9-136.0) respectively. During administration of GHRP-6, the only side effects observed were flush symptoms. CONCLUSIONS: Peak GH levels below 7 microg/l for the GHRP-6 test and below 13 microg/l for the combined GHRP-6+GHRH test identified all patients with GH deficiency correctly as defined by ITT. The results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.

scholarly journals The Diagnosis of Partial Growth Hormone Deficiency in Adults with a Putative Insult to the Hypothalamo-Pituitary Axis

2007 ◽  
Vol 92 (5) ◽  
pp. 1705-1709 ◽  
Author(s):  
Robert D. Murray ◽  
Martin Bidlingmaier ◽  
Christian J. Strasburger ◽  
Stephen M. Shalet
Keyword(s):  
Tolerance Test ◽  
Hormone Deficiency ◽  
Controlled Study ◽  
Control Group ◽  
Pituitary Hormone ◽  
Cross Sectional ◽  
Arginine Test ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Stimulation Tests

Abstract Context: Similar to patients with severe GH deficiency (GHD), those with a more moderate impairment of GH secretion [GH insufficiency (GHI)] have abnormal body composition, dyslipidemia, and insulin resistance. Given the inherent problems in the diagnosis of severe GHD, the situation is likely to be even more difficult in individuals with GHI. Objective: The objective of the study was to examine the utility of GH stimulation tests and GH-dependent proteins in the diagnosis of GHI. Design: The study was a cross-sectional, case-controlled study. Patients: The study included 31 patients with GHD, 23 with GHI [peak GH 3–7 μg/liter (9–21 mU/liter)], and 30 age- and sex-matched controls. Main Outcome Measures: Demographic and biochemical markers of GH status were measured. Results: Nineteen of the patients with GHI (83%) had no additional anterior pituitary hormone deficits. Ten GHI patients showed discordant GH status based on the two GH stimulation tests performed. GH status was defined by the highest peak GH value achieved; in four this was to the insulin tolerance test (ITT), four the arginine test, and two the GHRH-arginine test. In five of the six patients in whom GH status was not defined by the ITT, peak GH levels to the ITT were in the range 2.4–2.9 μg/liter. IGF-I values for the GHI adults were significantly lower than the control subjects (121 ± 48 vs. 162 ± 75 μg/liter; P &lt; 0.05); however, only six (26%) had values below the 10th percentile of levels seen in the control group. IGF binding protein-3 and acid labile subunit levels of the GHI adults were not significantly different from the controls. Conclusion: The diagnosis of GHI in an individual is extremely difficult because the patients rarely exhibit additional pituitary hormone deficits, and levels of GH-dependent proteins are normal in the majority. Diagnosis relies heavily on GH stimulation tests and requires two tests in all patients to define GHI; obesity when present is potentially a major confounder.

scholarly journals High Risk of Adrenal Insufficiency in Adults Previously Treated for Idiopathic Childhood Onset Growth Hormone Deficiency

2003 ◽  
Vol 88 (12) ◽  
pp. 5784-5789 ◽  
Author(s):  
Martin Lange ◽  
Ulla Feldt-Rasmussen ◽  
Ole Lander Svendsen ◽  
Knud William Kastrup ◽  
Anders Juul ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Hormone Deficiency ◽  
Childhood Onset ◽  
Gh Treatment ◽  
Insulin Tolerance ◽  
Igf I ◽  
Synacthen Test ◽  
Previously Treated

Abstract The aim was to reevaluate a group of adults treated for idiopathic childhood onset GH deficiency (GHD) after 18 yr without GH treatment. Twenty-six (11 females) patients participated. All but two had isolated GHD. Childhood diagnosis was established by insulin tolerance test (ITT). The patients were retested with an ITT to evaluate adult GH status. In five patients, an arginine and a synacthen test were performed instead of an ITT. Eleven of 25 patients had a subnormal cortisol response to ITT or synacthen. Ten patients had a GH peak less than 3.0 μg/liter (0.5. ± 0.5 μg/liter), whereas 16 patients displayed a normal GH response (12.3 ± 10.6 μg/liter) after ITT. IGF-I values were decreased in the patients with a pathological retest as well as in patients with a normal GH response compared with controls (P &lt; 0.005). In 26 idiopathic childhood onset GHD patients, 44% of the patients had developed adrenal insufficiency; 38.5% had persistent GHD in adulthood, using the same test in both childhood and adulthood. Patients having a normal GH test had decreased IGF-I levels, compared with controls, indicating impaired function of a seemingly normal GH axis. It is imperative that pituitary axes other than the GH axis are tested at regular intervals, even in the absence of GHD in adulthood.

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