Diagnostic Value Of Provocative Test By Insulin Combined With Clonidine In Short Stature Children

Objective: With the increasing people's standard of living and healthawareness, short stature gradually attracted people's attention. Short stature isthat height falls bellow-2SD or the3rd percentile of the normal populationstandard with same race,sex and age. Growth hormone deficiency(GHD) isan important cause of short stature, the prevalence rate is about28.4%. TheGH provocative test continues playing an important role in the diagnosis ofGHD. However, the classical provocative test is needed to be done in twodays, by using two drugs with different action mechanism, then blood samplesare drawn from a vein after administration of0,30,60,90,120minrespectively, for GH determination. It needed more times of blood collecting,caused much more pain and lager cost. At present, some researchers havebeen investigating the easier and safer combined provocative test. In our study,we try to test the children with short stature by insulin+clonidine, to evaluatethe diagnostic value to GHD and the etiological diagnosis of the shortchildren.Subjects and Methods:1. Patients: Eighty children (58boys and22girls), aged10.6±3.3(mean±SD)years, with short stature was studied during June2011to January2012. Theparticipants were recruited from the Department of Pediatrics, of the ThirdHospital of Hebei Medical University。The preclude criteria were absent ofhypothyroidism,small for gestational age,Turner syndrome,malnutrition andkidney disease and other chronic diseases2. Group：According to the clinical diagnosis all patients were divided intotwo groups (GHD group and Non-GHD group). The GHD group consisted of31patients,9girls and22boys, median age11.4years (4.5to16.9years).NGHD group consisted of49patients,13girls and36boys, median age10.2 years (range3.8to16years)3. Methods: Insulin+clonidine combined provocative test (0.075U/kgintravenously and4μg/kg orally respectively) was performed in allparticipants in GH assessment. Testing was performed at8:00am after anovernight fast.Blood samples (2~3ml) were drawn at baseline and30,60,90and120min after ingestion of clonidine and intravenous injection ofregular insulin for measuring the GH and Blood glucose. Blood sugardropped to50%baseline or less than3.8mmol/L is an effective provocation.Serum GH was measured by a commercial radioimmunoassay kit provided bythe Beijing north institute of biological technology,operated in strictaccordance with the instructions by using γ-radiation immunity counters.4. Statistical analysis: All statistical analyses were performed with SPSSsoftware, v17.0(SPSS Inc, Chicago, Illinois), graphs were made withExcel2003software. Data were presented as mean±SD, unless otherwisestated. Differences between GHD and NGHD children were assessed via theindependent samples t-test. The statistical significance level was set at5%(2-tailed).Results:1. Comparison of clinical data between GHD group and NGHD groupThe age,bone age,height,weight and BMI matched between two groups,there was no significant difference (P>0.05); the difference between bone ageand chronological age was (-2.62±1.21) years in GHD group,(-0.68±0.86)years in NGHD group, there was significant difference between two groups (P<0.05).2GH peak concentrationThe mean peak GH concentration was (6.47±4.54) μg/L(0.01~18.20μg/L) in group GHD,and (15.57±6.56) μg/L (5.77~29.13μg/L) ingroup NGHD, The mean peak GH concentration in group NGHD wassignificantly higher than that in group GHD (P<0.05).3GH peak time distribution of the combined provocative testThe percentage of the peak, appeared in0,30,60,90and120min was respectively6%,16%,48%,23%,7%in GHD group,2%,20%,45%,31%,2%in NGHD group,and4%,19%,46%,27%,4%.in GHD group+NGHD group.The GH peak time distribution between the combinedprovocative test and the classical single-drug provocation test was similar.4The sensitivity, specificity, coincidence of the combined provocative testThe GH peak concentration distribution in GHD group:<5μg/L13cases (42%),5~10μg/L11cases (35%),>10μg/L7cases (23%). The GHpeak concentration distribution in NGHD group:<5μg/L0cases (0%),5~10μg/L9cases (18%),>10μg/L40cases (82%). The sensitivity was77%, specificity was81%, the coincidence of the combined provocative testwith the clinical diagnosis was80%.5Adverse reactionsOne (1.25%) patient was observed with hypoglycaemic reaction such asdizziness, palpitation, sweating, and relieved after symptomatic treatment. Noother adverse reactions were observed.Conclusions:1. The provocative test by insulin combined with clonidine is a good methodfor the etiological diagnosis of short stature children, it has advantages, suchas simple,less times of blood collection, relieve the patient pain, lowerfinancial burden and high safety, etc.2. The provocative test by insulin combined with clonidine has a highsensitivity, specificity and accuracy rate in the diagnosis of GHD andNGHD.3. The emergence time of GH peak concentration between the combinedprovocation test with the classical single-drug provocation test are similar, sothe combined provocation test could be used in short stature children as areplacement of the traditional single-drug provocation test.4In the insulin+clonidine provocation test, there may be the phenomenonof over provocation, in some GHD patients, further diagnosis for them wereneeded; there may be the phenomenon of over-diagnosis of GHD, in someNGHD patients, regular monitoring of growth and development indicators in them are needed, if necessary, redetermination of serum GH levels.