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 (<25%) pre-test GHD probability could be predicted when IGF-I SDS > +0.91 in the presence of other pituitary deficits or IGF-I SDS > -0.52 in the absence of other pituitary deficits. A high (>75%) pre-test GHD probability could be predicted when IGF-I SDS < -0.82 in the presence of other pituitary deficits or IGF-I SDS < -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 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 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 The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: A comparison

2013 ◽  
Vol 60 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Yasuyuki Kinoshita ◽  
Atsushi Tominaga ◽  
Satoshi Usui ◽  
Kazunori Arita ◽  
Tetsuhiko Sakoguchi ◽  
...  
Keyword(s):  
Gh Deficiency ◽  
Japanese Patients ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Insulin Tolerance ◽  
Adult Gh Deficiency

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 GH deficiency in patients after cure of acromegaly by surgery alone

2011 ◽  
Vol 165 (6) ◽  
pp. 873-879 ◽  
Author(s):  
Shozo Yamada ◽  
Noriaki Fukuhara ◽  
Hiroshi Nishioka ◽  
Akira Takeshita ◽  
Hisanori Suzuki ◽  
...  
Keyword(s):  
Large Scale ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Stimulation Test ◽  
Oral Glucose ◽  
Japanese Adult ◽  
Preoperative Serum ◽  
Stimulation Tests ◽  
Design And Methods ◽  
Deficient Group

ObjectiveThe aim of this study was to determine the frequency and characteristics of severe GH deficiency (sGHD) in patients after treatment of acromegaly by surgery alone.Design and methodsOne hundred and eighty-six patients fulfilling the criteria for cure of acromegaly were examined by GH-releasing peptide-2 stimulation test or arginine stimulation test as well as oral glucose tolerance test (GTT). In addition, the Japanese adult hypopituitarism questionnaire was completed to determine the quality of life (QoL).ResultssGHD was found in 17 patients (9.1%; the GH-deficient group), and not found in 169 patients (90.9%; the GH-sufficient group). There were no significant differences in preoperative serum GH levels, IGF1 levels, incidence of hyperprolactinemia, tumor volumes, or incidence of microadenoma between the two groups. Upon follow-up examination, IGF1 levels and Z-scores of IGF1 levels were significantly lower in the GH-deficient group than in the GH-sufficient group, whereas neither basal GH levels nor nadir GH levels during 75 g GTT were significantly different between the two groups. Moreover, sGHD patients had a substantially higher incidence of multiple pituitary failures (17.6 vs 2.4%) and dyslipidemia (60 vs 16.2%). sGHD patients had a substantially poorer condition-related QoL.ConclusionsThis is the first large-scale, single-center, clinical study to evaluate sGHD in patients after cure of acromegaly by surgery alone. This study found that sGHD occurred in ∼9% of patients and assessment of GHD by stimulation tests is critical after successful treatment of acromegaly by surgery.

scholarly journals SUN-307 Partial Secondary Adrenal Insufficiency and Growth Hormone Deficiency in Fibromyalgia

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lucinda Gruber ◽  
Sanjeev Nanda ◽  
Todd B Nippoldt ◽  
Alice Y Chang ◽  
Irina Bancos
Keyword(s):  
Adrenal Insufficiency ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Cortisol Concentration ◽  
Stimulation Test ◽  
Gh Replacement ◽  
Insulin Tolerance ◽  
Morning Cortisol ◽  
Cosyntropin Stimulation Test

Abstract Introduction: Low or borderline cortisol concentrations and impaired response to dynamic testing have been reported in patients with fibromyalgia, potentially related to hypothalamus-pituitary dysfunction.1,2 Superimposed adrenal insufficiency (AI) may contribute to some fibromyalgia symptoms or delay improvement in patients enrolled in fibromyalgia treatment programs. We hypothesized that a subset of patients with fibromyalgia have: 1) partial secondary AI and concomitant growth hormone (GH) deficiency 2) a discordance in Cosyntropin stimulation test and 3) improvement in fibromyalgia symptoms with initiation of glucocorticoid and/or GH replacement. Design: This was a retrospective study of patients with fibromyalgia diagnosed with partial secondary AI based on abnormal insulin tolerance test (peak cortisol &lt; 18 mcg/dL) at our institution from June 2002 to August 2019. Patients were excluded if they had other reasons for adrenal insufficiency, including steroid exposure and opioid use. Results: We identified 22 patients (18 women, 82%) diagnosed with partial AI at a median age of 38 years (range 19-65). The fibromyalgia symptoms included fatigue (n=22, 100%), pain (n=22, 100%), sleep disturbance (n=15, 68%), and bowel changes (n=13, 59%). The median morning cortisol concentration was 8.6 mcg/dL (range 1.1-11); 9 patients (41%) had a morning cortisol concentration below the normal range (7 mcg/dL). The median ACTH level was 15.5 pg/mL (range 7.7-54). Nineteen patients had baseline IGF1 levels, with a median z-score of -0.94 (range -1.96 to 1.70). MRI pituitary imaging was performed in 20 patients and showed no significant pituitary pathology. All patients achieved hypoglycemia &lt;=40 mg/dL during the insulin tolerance test. Peak median cortisol level was 11 mcg/dL (range 5.4-17). Nineteen patients (86%) also had partial GH deficiency (defined as a peak GH &lt; 4 ng/mL) with a median GH level of 0.36 ng/mL (range 0.03-3.83). Cosyntropin stimulation test was performed in 13 patients (59%) with a 1 mcg dose in 2 patients and 250 mcg dose in 11 patients. The peak cortisol was &gt;=18 mcg/dL in 10 (77%) patients. All patients were started on physiologic glucocorticoid replacement, and 12 patients were started on GH replacement. Endocrinology follow-up information was available for 13 patients, and 8 (62%) reported symptom improvement after starting treatment. Conclusions: Patients with fibromyalgia can have co-existing partial secondary AI and GH deficiency as defined by insulin-induced hypoglycemia. Cosyntropin stimulation test can be used in patients with fibromyalgia, but a normal test does not rule out partial secondary AI. Replacing the underlying deficiency improved symptoms in some patients demonstrating certain fibromyalgia symptoms may overlap with AI and GH deficiency. 1Gur et al. Ann Rheum Dis. 2004. 63(11):1504-1506. 2Kirnap et al. Clin Endocrinol (Oxf). 2001. 55(4):455-459.

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.

scholarly journals THE CUT-OFF LIMITS OF GH RESPONSE TO INSULIN TOLERANCE TEST RELATED TO BODY MASS INDEX FOR THE DIAGNOSIS OF ADULT GH DEFICIENCY

2020 ◽  
Author(s):  
Valentina Gasco ◽  
Alice Ferrero ◽  
Alessandro Bisceglia ◽  
Nunzia Prencipe ◽  
Valeria Cambria ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Mass ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Insulin Tolerance ◽  
Adult Gh Deficiency

scholarly journals Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak

2013 ◽  
Vol 168 (5) ◽  
pp. 733-743 ◽  
Author(s):  
Ulla Feldt-Rasmussen ◽  
Georg Brabant ◽  
Dominique Maiter ◽  
Björn Jonsson ◽  
Andy Toogood ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Pituitary Hormone ◽  
Gh Treatment ◽  
Gh Replacement ◽  
Phenotypic Response ◽  
Waist Hip Ratio ◽  
Insulin Tolerance ◽  
Stimulation Tests

ObjectiveWe studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv) IGF1 SDS after 24 months of GH replacement or v) ΔIGF1 SDS from baseline to 24 months was related to the phenotypic response to GH treatment.Design, patients, and measurementsThe patient cohort (n=1752; 50% women) was obtained from KIMS (Pfizer International Metabolic Database). The patients were divided into three groups of approximately equal size (tertiles) according to the stimulated GH-peak values and baseline IGF1 SDS and were studied at baseline, 12, and 24 months of GH therapy.ResultsLower baseline IGF1 SDS predicted better response in weight, BMI, total cholesterol, and triglycerides, while IGF1 SDS after 24 months was associated with reduction in waist/hip ratio, total cholesterol, and improved quality of life (QoL). Age-correlated negatively with the response in body weight, BMI, waist, IGF1 SDS, and total and LDL-cholesterol.Response in weight and BMI was greater in men than in women, whereas women showed greater improvement in QoL than men. Patients with more severe GHD as assessed by lower GH-peaks and more pituitary hormone deficiencies had a greater increase in IGF1 SDS. The increase in IGF1 SDS was associated with a reduction in waist/hip ratio and an increase in weight, BMI, and triglycerides. There was no correlation with other lipids, blood pressure, or glucose.ConclusionOur findings indicate that baseline and 24 months, IGF1 and its degree of increase during GH replacement were more important than stimulated peak GH to predict the phenotypic response.

Sign in / Sign up

Export Citation Format

Share Document