Test Of Growth Hormone Secretion Research Articles

IGF-1 and IGFBP 3 in Growth Hormone Deficiency Role of Insulin Like Growth Factor-1 (IGF-1) and IGF Binding Protein 3 in the Diagnosis of Growth Hormone Deficiency: Changing Paradigm

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. Serum IGF-I levels are monitored during GH replacement treatment in subjects with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GHrelated side-effects. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 hours and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. We hereby review the various literatures at disposal justifying the use of IGF-1 and IGBP3 for diagnosis of growth hormone deficiency.Data Source: We searched PUBMED and MEDLINE database for relevant articles including key words. References of each article were further reviewed for final synthesis of the manuscript.J Nepal Paediatr Soc 2012;32(2):154-162 doi: http://dx.doi.org/10.3126/jnps.v32i2.5342

Determine the Need for Growth Hormone Secretion Tests after Radiotherapy based on Hypothalamus Dose, IGF1, and BMI

Determine the Need for Growth Hormone Secretion Tests after Radiotherapy based on Hypothalamus Dose, IGF1, and BMI

Influence of gender, age, body mass index, abdominal fat and serum levels (HDL-C, glucose, triglycerides, IGF-1) on growth hormone (GH) response to GH-releasing hormone plus arginine and insulin tolerance tests / Einfluss von Geschlecht, Lebensalter, BMI, Bauchumfang und laborchemischen Parametern (HDL-C, Glukose, Triglyzeride, IGF-1) auf den Wachstumshormon-Anstieg nach der Durchführung eines GHRH+Arginin- und eines Insulin-Toleranz-Tests

Abstract Background: Diagnosis of growth hormone (GH) deficiency in adulthood is established by provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard, whereas the combined GH-releasing hormone (GHRH) plus arginine (GHRH+ARG) test is considered the best alternative to the ITT. The aim of the present study was to correlate the degree of the GH response to the GHRH+ARG test and to the ITT and to assess the influence of gender, age, body mass index (BMI), abdominal circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, serum glucose and insulin-like growth factor 1 (IGF-1) to the GH response. Methods: A total of 50 adult patients (25 men, 25 women) aged 18–74 years were studied. BMI and abdominal circumference were measured. Basal blood samples were taken for IGF-1, HDL, glucose and triglycerides. All subjects underwent GH provocation with both the GHRH+ARG test and the ITT. Results: Peak GH response was significantly higher (men/women: p<0.01) after GHRH+ARG than with ITT, with a strong positive correlation between the peak GH responses in both tests (r=0.753, p<0.01). Peak GH response to ITT and to GHRH+ARG was significantly higher in females than in males (ITT, p=0.01; GHRH+ARG, p<0.01). A significant negative correlation was found between the peak GH response after ITT and GHRH+ARG and age (ITT, r=−0.322; GHRH+ARG, r=−0.281). There was also a significant negative correlation between peak GH response to GHRH+ARG and BMI (r=−0.332) and abdominal circumference (r=−0.388). Peak GH response was positively correlated with plasma IGF-I levels in both tests (ITT, r=0.437; GHRH+ARG, r=0.346). On the basis of the GH response to both GH provocation tests, the subjects were divided into two groups: group 1, subjects with severe GH deficiency (23 patients with GH peak ≤3 μg/L in ITT and ≤9 μg/L in GHRH+ARG); group 2, subjects with slight or without GH deficiency (27 subjects with GH peak >3 μg/L in ITT and >9 μg/L in GHRH+ARG). In group 1 patients, plasma IGF-I concentrations were lower than in group 2 (p=0.019) and there were significantly older (p=0.042) and more male (p=0.0041) patients in group 1. No significant difference was found for BMI, abdominal circumference, HDL, glucose and triglyceride levels between the two groups. Conclusions: The results of the present study indicate that the degree of the GH response to ITT and GHRH+ARG is correlated with age and plasma IGF-I levels. There is a correlation between peak GH after GHRH+ARG and BMI as well as abdominal circumference. Therefore, age-, gender- and BMI-related test specific cut-off points are required.

Advances in the Understanding of Adult Growth Hormone Deficiency Syndrome – Diagnosis, Epidemiology and Management

In patients with hypopituitarism, growth hormone (GH) deficiency is almost always present. Lack of other pituitary hormones may require prompt replacement, but lack of GH is also associated with several abnormalities, which can be improved by GH treatment. The aberrations include low bone mass and increased risk of fractures, abnormal body composition, e.g. increased fat mass and reduced lean body mass resulting in reduced muscle mass and strength. Decreased exercise capacity may be influenced by impaired cardiac performance and heat intolerance. Increased abdominal fat results in metabolic disturbancies, such as reduced insulin sensitivity and hyperlipidaemia, increasing the risk of cardiovascular diseases. Patients with hypopituitarism replaced with relevant hormones except GH have increased mortality due to cardiovascular diseases and increased morbidity. Thus, it is important to diagnose GH deficiency, which requires precise diagnostic criteria and methods. Dynamic testing of GH secretion with an insulin tolerance test or arginine plus GH-releasing hormone can be used.

Exercise Provocation Test for Growth Hormone Secretion: Methodologic Considerations

The diagnosis of Growth Hormone (GH) deficiency in children with short stature is complex, and in certain cases, might be very difficult. Most of the provocative tests used to evaluate GH deficiency use pharmacological agents. The artificial nature of the pharmacological tests and the possibility that these tests might not always reflect GH secretion under normal physiological conditions provides the impetus for a more physiologic test. Exercise is one of the important GH releasing physiological stimuli. This review will summarize the current knowledge on the methods for performing laboratory exercise provocation test for GH secretion in children. In addition to recommendations of more standardized exercise protocols and environmental considerations, we will also focus on GH responses to exercise in unique populations such as obese children.

The management of adult growth hormone deficiency syndrome

Background: In patients with hypopituitarism, growth hormone deficiency (GHD) is almost inevitably present. Lack of other pituitary hormones may require prompt replacement, but lack of growth hormone (GH) is also associated with several abnormalities. Growth hormone treatment safely improves or normalizes many of these deviations. Results: The aberrations include low bone mass and increased risk of fractures, abnormal body composition in terms of increased fat mass, and reduced lean body mass resulting in reduced muscle mass and strength. The decreased exercise capacity in GHD may be influenced by impaired cardiac performance and heat intolerance. Increased abdominal fat results in metabolic disturbancies such as reduced insulin sensitivity and hyperlipidemia, leading to an increased risk of cardiovascular diseases. Patients with hypopituitarism who have had relevant hormones replaced except GH have increased mortality due to, for example, cardiovascular diseases. Conclusions: Thus, it is important to diagnose GHD, which requires precise diagnostic criteria and methods. Dynamic testing of GH secretion with insulin tolerance test or arginine + GH releasing hormone can be used. Patients with childhood onset GHD should be re-evaluated if GH therapy is maintained into adulthood. Although GH replacement therapy improves the patophysiological manifestations of GHD and quality of life, it is unclear whether mortality is reduced.

Acromegaloidism with normal growth hormone secretion associated with X-Tetrasomy

We reported a case of a 26-year-old female who was referred to our clinic with the diagnosis of possible acromegaly. She was born from a term pregnancy by forceps delivery. The patient was diagnosed as having hip luxation at one month and spoke her first word at 15 months. She had been diagnosed at the age of 9 years old as having perinatal encephalopathy with intellectual and motor affectation. Since this period of time she has undergone an insidious change in her appearance, mainly comprising progressive coarsening of the face. For this reason she was submitted to our clinic with presumed acromegaly. Dynamic tests of growth hormone secretion ruled out such a diagnosis. The Patient was considered as having "acromegaloidism", a term used for patients whom manifest clinical features of acromegaly but do not present a demonstrable growth hormone hypersecretion. Subsequently cytogenetic evaluation revealed an infrequent chromosome pattern: X-Tetrasomy. In the present article a differential diagnosis of acromegaloidism and the potential role of genes present on X-chromosome involved in human growth such as SHOX gene are discussed. Overdosification of SHOX gene might explain tall stature of girls with X-tetrasomy. Our observation suggested that X-tetrasomy should be considered in the differential diagnosis of acromegaloidism. Furthermore, this may lead to the identification of new genes in the X-chromosome that are important for growth of facial structures.

A Case of Gitelman's Syndrome with Short Stature

We report the case of an 8-yr-old girl with short stature. Her height was -2.65 SD and blood examination revealed hypokalemia (2.9 mEq/l), hypomagnesaemia, hypocalsiuria (Ca/Cr=0.0039) and metabolic alkalosis (pH 7.454, HCO3- 24.9 mmol/l). For differential diagnosis between Gitelman's syndrome (GS) and Bartter syndrome (BS), we performed the loop diuretic furosemide (FUR) test and hydrochlorothiazide (HCT) double dose (2 and 4 mg/kg) test. Even the higher dose of HCT induced significantly lower increase of urinary Na and Cl excretions than the FUR. Growth hormone (GH) secretion tests (insulin and arginine) revealed GH deficiency. In addition to growth hormone injection, administration of Mg and spironolactone was started. After the replacement therapy started, the girl's height gain was improved (9.7 cm/yr) and her serum potassium became within the reference range. One year after GH replacement therapy was performed and GH replacement therapy was discontinued for two months, and GH secretion tests (insulin and arginine) showed GH deficiency again. We discussed previous reports of the clinical signs and test results of GS with regard to the relation between hypokalemia, hypomagnesemia and short stature.

Growth Hormone (GH) Peaks versus Areas Under the Curve in the Diagnosis of Adult GH Deficiency: Analysis of the Variables Provided by the GHRH + GHRP-6 Test

The diagnosis of growth hormone deficiency (GHD) relies on provocative tests of GH reserve. The aim in these tests is to obtain an objective, biochemical-based, measure of gland function, but clinicians and researchers rely on the GH peak, as a surrogate of the 24-hour pituitary secretion. However, on a mathematical basis the area under the secretory curve (AUC) should be more valid for this evaluation. To validate which variable provided by a provocative test of GH secretion is mathematically more robust for supporting the clinical diagnosis. Adult normal subjects and GHD patients were challenged with the combined stimulus GHRH + GHRP-6. The diagnostic efficacy of the GH peak, and the AUC were compared by the receiver operating characteristic (ROC) curve methodology. 146 patients with GH deficiency due to organic pituitary disease and 184 healthy subjects were administered GHRH 1 microg/Kg iv, plus GHRP-6 1 microg/Kg iv, and GH was determined. Four variables were studied: (a) the GH peak; (b) the "standard" AUC, (c) the "stimulated" AUC and (d) the basal value, used as internal control. Under ROC curve analysis, the basal variable was devoid of diagnostic capability, while the other variables performed strikingly well, the ROC curve area for the GH peak was 0.9997; and for the AUC 0.9993, with no statistical differences. The variables provided by measuring the GH peak and the area under the curve were similarly effective for diagnosis, although on clinical grounds, the peak was more convenient as needed no calculation. If results for other test were similar the time-honored method of measuring the GH peak could be considered mathematically validated.

Neuropharmacological assessment of growth hormone secretion.

The biochemical diagnosis of individuals who are either deficient in growth hormone (GH) or who have alterations in the normal pattern of GH secretion is difficult. The uncertainty surrounding diagnosis reflects the lack of a thorough understanding of the physiology of GH secretion and of the hypothalamic hormones involved. At least three hormones are implicated: GH-releasing hormone (GHRH), somatostatin and the endogenous ligand of the GH secretagogue receptor, although the role that each plays in the release of GH is not clear from the available experimental evidence. In such a situation, most of the dynamic tests of GH secretory capacity in humans need to undergo a 'trial and error' process before being validated. The search for the 'gold standard' test of GH secretion is ongoing, and the combination of GHRH plus GH secretagogues will probably play an important role in future clinical diagnosis.

Overnight growth hormone concentrations are usually normal in pubertal children with idiopathic short stature--a Clinical Research Center study.

To estimate the incidence of low growth hormone (GH) concentration in children and adolescents with idiopathic short stature, overnight GH levels were measured in 167 subjects. The results were compared with data from 132 normal children of similar pubertal stage, bone age, or body mass index. The majority of short children had normal overnight GH concentrations in a distribution not significantly different from that observed in normal children. However, in 6% of children grouped by pubertal stage and in 13% of children grouped by bone age, overnight GH levels were below the 95% confidence limits of normal. The overnight GH levels were above normal in 6%. The observed frequencies of both low and high GH levels were significantly greater than expected (P < 0.001). However, when body mass index was included in the analysis, only 5% of the children had low GH measures, and only 4% had high GH measures (both not significant). This frequency of low overnight GH levels in short children is considerably less than that reported by others. Thus, these data do not support the hypothesis that a deficiency of spontaneous GH secretion is a common cause of short stature. We conclude that standard GH stimulation tests, despite their limitations, remain the best definitive test of GH secretion. Subsequent overnight GH studies may be useful, however, in selected clinical settings such as previous cranial irradiation or other central nervous system disorder.

Reproducibility and Comparison of Growth Hormone Secretion Tests

To assess the degree of reproducibility of spontaneous GH secretion and pharmacological tests we studied 15 prepubertal children with short stature and abnormal growth rate. In all children, spontaneous overnight GH secretion was measured followed by a clonidine test in 8 children and an arginine test in the remaining 7. The same protocol was repeated a week later. Intra-individual variability of GH secretion in both physiological and pharmacological tests was expressed as the coefficient of variation (CV%). No significant difference was found between the first and second value of parameters of spontaneous GH secretion. Maximum spontaneous GH peak (MS) and mean 12-h GH concentration (MGH) correlated significantly (r = 0.78, p < 0.001). Mean CV% of all parameters of repeated GH profiles (around 30%) were lower than those of provocative tests (around 70%) (p < 0.05). No significant difference was found between CV% of clonidine and arginine tests. There was no correlation between MGH or MS and GH response to provocative test in the same child. We found a significant correlation between the log transformed maximum provocative GH response to the arginine test and the length of the time interval (in min) from the end of the last GH peak in the previous profile to the time zero of the provocative test (r = 0.60, p < 0.05). This relationship was not found for the clonidine test. We conclude that spontaneous GH secretion in children with short stature is more reproducible than stimulated GH response with a week's difference. Perhaps the higher variability of provocative GH secretion may be related to the state of the endogenous hypothalamic rhythm of both GHRH and somatostatin release at the time of the test.

Test of growth hormone secretion in adults: poor reproducibility of the insulin tolerance test.

The insulin tolerance test (ITT) is regarded as the most reliable provocative test in the diagnosis of growth hormone (GH) deficiency in adults. In the present study the test was evaluated by investigating the range of GH responses in normal adult males and females and the intra-individual reproducibility of the test. Sixteen healthy non-obese adults, eight males (median age 31.5 years) and eight females (median age 31.8 years) were tested twice with the ITT, with a minimum of 72 h between each test. The females were tested between day 3 and day 10 of their menstrual cycles. Adequate hypoglycemia was achieved in all cases with a median nadir blood glucose of 1.3 mmol/l (range 0.8-2.0). Growth hormone in serum was measured by immunoradiometric assay and low values were confirmed by a different assay. Median peak GH concentration responses to the ITT were: in males 27.9 micrograms/l, range 5.0-71.1 (test 1) and 30.5 micrograms/l, range 7.9-69.5 (test 2); and in females 9.0 micrograms/l, range 4.1-17.9 (test 1) and 8.4 micrograms/l, range 0.09-42.4 (test 2). The rise in GH concentration during the ITT was higher in males than in females. In the males, all stimulated GH values were > or = 5.0 micrograms/l. In the females, four out of 16 tests gave values below 5.0 micrograms/l and in one test the GH value was around the detection limit of the assays. There was poor reproducibility during repeated testing, with no correlation between the results of the two tests. The results did not correlate to the magnitude of the hypoglycemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Is there a place for urinary growth hormone measurement?

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

Hazards of tests of growth hormone secretion.

Hazards of tests of growth hormone secretion.

Hazards of pharmacological tests of growth hormone secretion.

Hazards of pharmacological tests of growth hormone secretion.

Hazards of pharmacological tests of growth hormone secretion.

Hazards of pharmacological tests of growth hormone secretion.

Hazards of pharmacological tests of growth hormone secretion in childhood.

Hazards of pharmacological tests of growth hormone secretion in childhood.

Growth and Growth Hormone Therapy in Hypochondroplasia

The growth of 84 patients with hypochondroplasia (56 male, 28 female) was studied. A wide spectrum of severity was found from quite severe short limbed dwarfism to short apparently normal prepubertal children who manifested disproportion only at puberty when growth failed. The onset of puberty was at the normal time but the pubertal growth spurt appeared not to materialize and it is this lack which resulted in severely compromised adult heights of 145-165 cm in boys and 133-151 cm in girls. Twenty (12 M, 8 F) hypochondroplastic children aged between 4.3 and 12.8 years were recruited to a study of the effects of biosynthetic growth hormone. All had normal growth hormone responses (greater than 15 mU/l) to a pharmacological test of growth hormone secretion. Biosynthetic growth hormone in doses between 12-32 mu/m2/week produced a significant acceleration in height velocity standard deviation score (SDS) for chronological age (CA) from a pretreatment mean of -1.66 (SD 1.36) to +1.62 (SD 1.52) (p less than 0.001). Significant increases were also observed in the height SDS for bone age (BA), sitting height (SH) SDS and subischial leg length (SILL) SDS. A longer period will be required to assess the effect of treatment on adult height prognosis.

Pharmacological Testing of Growth Hormone Secretion

The laboratory confirmation of growth hormone (GH) deficiency (GHD) has been extensively studied. Multiple stimuli induce GH release, but insulin-induced hypoglycemia usually is considered the 'gold standard'. Seventy-five to 90% of normal children have significant increments of hGH to any single test. Complete and partial syndromes of GHD have been defined, but some patients with a clinical appearance of GHD release hGH during provocative testing. Discordant results on varied tests may occur in the same child. Sequential and simultaneous tests have been attempted with diverse time patterns; testing sequence may significantly affect data interpretation. Persistent problems with GH provocative tests remain: normal data not strictly defined throughout childhood, multiple tests with discordant results, and substantial discrepancies of immunopotency estimates with different radioimmunoassays. Some children with 'normal' hGH increments during provocative tests, despite clinical GHD, may require short-term treatment with hGH to finally establish the diagnosis.