Pharmacological Stimulation Tests Research Articles

Development and Validation of a Prediction Rule for Growth Hormone Deficiency Without Need for Pharmacological Stimulation Tests in Children With Risk Factors.

IntroductionPractice guidelines cannot recommend establishing a diagnosis of growth hormone deficiency (GHD) without performing growth hormone stimulation tests (GHST) in children with risk factors, due to the lack of sufficient evidence.ObjectiveOur goal was to generate an evidence-based prediction rule to diagnose GHD in children with growth failure and clinically identifiable risk factors.MethodsWe studied a cohort of children with growth failure to build the prediction model, and a second, independent cohort to validate the prediction rule. To this end, we assessed the existence of: pituitary dysgenesis, midline abnormalities, (supra)sellar tumor/surgery, CNS infection, traumatic brain injury, cranial radiotherapy, chemotherapy, genetic GHD, pituitary hormone deficiencies, and neonatal hypoglycemia, cholestasis, or hypogenitalism. Selection of variables for model building was performed using artificial intelligence protocols. Specificity of the prediction rule was the main outcome measure in the validation set.ResultsIn the first cohort (n=770), the resulting prediction rule stated that a patient would have GHD if (s)he had: pituitary dysgenesis, or two or more anterior pituitary deficiencies, or one anterior pituitary deficiency plus: neonatal hypoglycemia or hypogenitalism, or diabetes insipidus, or midline abnormalities, or (supra)sellar tumor/surgery, or cranial radiotherapy ≥18 Gy. In the validation cohort (n=161), the specificity of the prediction rule was 99.2% (95% CI: 95.6–100%).ConclusionsThis clinical rule predicts the existence of GHD with high specificity in children with growth disorders and clinically identifiable risk factors, thus providing compelling evidence to recommend that GHD can be safely diagnosed without recurring to GHST in neonates and children with growth failure and specific comorbidities.

Growth hormone receptor polymorphisms and growth hormone response to stimulation test: a pilot study.

No gold standard pharmacological stimulation test exists for the diagnosis of growth hormone deficiency (GHD). In addition, the genetic factors that influence growth hormone (GH) responses remain unclear. This study aimed to determine whether polymorphisms in exon 6 of the GH receptor gene influence responses to the L-arginine GH stimulation test. This study included 27 prepubertal patients with confirmed GHD. GHD was defined as a peak GH level <8 ng/mL in response to pharmacological stimulation. The mean GH peak after L-arginine stimulation was 2.9±2.9 ng/mL. The included patients had the following genotypes at the third position of codon 168: AA (N.=1), AG (N.=15) and GG (N.=11). Patients carrying the AA and AG genotypes exhibited stronger responses to arginine than patients with the GG genotype (3.1±2.7 vs. 1.5±1.3 ng/mL, P=0.01). The approach employed in this study could elucidate GH profiles under physiological and pathological conditions, facilitating improved interpretation of pharmacological stimulation tests.

O Papel dos Testes de Estimulação Farmacológica no Diagnóstico da Deficiência de Hormona do Crescimento em Crianças e Adolescentes

The incidence of short stature associated with growth hormone deficiency has been estimated to be about 1:4000 to 1:10000. It is the main indication for treatment with recombinant growth hormone. The aims of the study were to evaluate the results of growth hormone stimulation tests and identify the growth hormone deficiency predictors. A cross-sectional, analytical and observational study was conducted. We studied all the children and adolescents submitted to growth hormone pharmacological stimulation tests between January 2008 and May 2012. Growth hormone deficiency diagnosis was confirmed by two negatives growth hormone stimulation tests (growth hormone peak < 7 ng/ml). The statistical analysis was performed using student t-test, chi-square, Pearson correlation and logistic regression. Statistical significance determined at the 5% level (p ≤ 0.05). Pharmacological stimulation tests were performed in 89 patients, with a median age of 10 [3-17] years. Clonidine (n = 85) and insulin tolerance test (n = 4) were the first growth hormone stimulation tests performed. Growth hormone deficiency was confirmed in 22 cases. In cases with two growth hormone stimulation tests, the growth hormone peak showed a moderate correlation (r = 0.593, p = 0.01). In logistic regression model height (z-score) and the growth hormone peak in first stimulation test were predictors of growth hormone deficiency diagnosis (each one unit increase in z-score decrease the growth hormone deficiency probability). Measurement of IGF-1 cannot be used in diagnosing growth hormone deficiency. Auxological criteria associated with a positive test seems to be a reliable diagnostic tool for growth hormone deficiency.

Approach to Testing Growth Hormone (GH) Secretion in Obese Subjects

Identification of adults with GH deficiency (GHD) is challenging because clinical features of adult GHD are not distinctive and because clinical suspicion must be confirmed by biochemical tests. Adults are selected for testing for adult GHD if they have a high pretest probability of GHD, ie, if they have hypothalamic-pituitary disease, if they have received cranial irradiation or central nervous system tumor treatment, or if they survived traumatic brain injury or subarachnoid hemorrhage. Testing should only be carried out if a decision has already been made that if deficiency is found it will be treated. There are many pharmacological GH stimulation tests for the diagnosis of GHD; however, none fulfill the requirements for an ideal test having high discriminatory power; being reproducible, safe, convenient, and economical; and not being dependent on confounding factors such as age, gender, nutritional status, and in particular obesity. In obesity, GH secretion is reduced, GH clearance is enhanced, and stimulated GH secretion is reduced, causing a false-positive result. This functional hyposomatotropism in obesity is fully reversed by weight loss. In conclusion, GH stimulation tests should be avoided in obese subjects with very low pretest probability.

Cut-off values of serum growth hormone (GH) in pharmacological stimulation tests (PhT) evaluated in short-statured children using a chemiluminescent immunometric assay (ICMA) calibrated with the International Recombinant Human GH Standard 98/574

Hospital de Pediatr i a Prof. Dr. Juan P. Garrahan, Combate de los Pozos 1881, Ciudad Autonoma de Buenos Aires, CP 1245, Argentina, Phone: +54 11 43084300, Fax: +54 11 43086700, mE- ail: echaler@yahoo.com Juan M. Lazzati, Mercedes Maceiras, Marco A. Rivarola and Alicia Belgorosky: Hospital de Pediatr i a Prof. Dr. Juan P. Garrahan , Buenos Aires , Argentina Gabriela Ballerini, Mauro Frusti, Ignacio Bergada and Gabriela Ropelato: Hospital de Ni n os Ricardo Gutierrez , Buenos Aires , Argentina

Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus–pituitary–adrenal (HPA) axis responses to a low-dose ACTH1–24 (Synacthen) and dexamethasone–CRH test in healthy school teachers

Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus–pituitary–adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30–64 years): a low-dose adrenocorticotrophic hormone (ACTH1–24, Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone–corticotropin releasing hormone (DEX–CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at − 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort–reward–imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX–CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

Pharmacological and Physiological Growth Hormone (GH) Stimulation Tests to Predict Successful GH Therapy in Children

Although the current use of growth hormone (GH) stimulation tests (GHSTs) is still subject to debate, the tests are widely used to diagnose GH deficiency. This literature review evaluates primarily the sensitivity, specificity and reliability of GHSTs and secondarily their convenience. Single pharmacological tests typically address only a single pathway in the complex physiological regulation of GH secretion and are therefore characterized by lower sensitivity, specificity and reliability than combined pharmacological tests or physiological tests. In spite of the high levels of sensitivity, specificity and reliability, physiological tests require considerably more effort to perform, from the physician as well as from the child. Therefore, a need for an alternative, convenient, physiological GHST still remains. Oral ingestion of dietary protein is convenient in practice and may induce more physiological stimulation of GH secretion, hence may be a promising valuable addition to the existing GHSTs in GH deficiency.

The advantage of measuring spontaneous growth hormone (GH) secretion compared with the insulin tolerance test in the diagnosis of GH deficiency in young adults

Reassessment of GH status after the attainment of adult height has important clinical implications in the diagnosis and prognosis of GH deficiency (GHD) in adulthood. The current GH threshold for biochemical definition of GHD in young adults is still a subject of debate. To investigate the role of pharmacological stimulation tests compared with spontaneous 12-h nocturnal GH secretion in the diagnosis of permanent GHD in young adults with childhood-onset GHD. Forty-five young adults (25 males, 20 females) with childhood-onset GHD, height standard deviation score (SDS) -1.1 +/- 1.3 and body mass index (BMI) SDS 1.0 +/- 1.6, were re-evaluated at the age of 19.8 +/- 2.7 years. Sixteen subjects showed a normal pituitary gland on magnetic resonance imaging (MRI), while in 29, consistent structural hypothalamic-pituitary abnormalities were found. GH secretion was assessed by means of an insulin tolerance test (ITT) and a 12-h spontaneous nocturnal profile as well as by IGF-I assessment. The results were compared with those of 43 healthy controls. Mean 12-h spontaneous nocturnal GH secretion was < 3.1 microg/l (the lowest limit of the normal range) in 36 (80%) of the subjects and > 3.1 microg/l in nine (20%). Of these 36 patients, 29 (80%) had abnormal MRI findings and 20 (55%) had multiple pituitary hormone deficiencies (MPHD). All nine subjects with mean spontaneous GH secretion > 3.1 microg/l had a normal pituitary MRI, isolated GHD and a peak GH response to ITT > 5 microg/l. There was a discordance in 14 patients (31%), who showed a peak GH response to ITT > 5 microg/l but a reduced spontaneous GH secretory capacity; 10 had structural hypothalamic-pituitary abnormalities on MRI. Although the ITT provides valuable information and proves to be a sensitive index of permanent GHD, the results of this study emphasize the potential diagnostic value of assessment of 12-h spontaneous GH secretion in young adults with childhood-onset GHD.

Serum leptin levels are not influenced by arginine and insulin infusion and by acute changes of GH.

The aim of this study was to evaluate the relationship between GH and leptin in a group of short children and adolescents. Leptin and GH serum levels were measured before and during pharmacological stimulation tests (arginine and insulin) in a group of 45 children (30 male, 15 female), mean age 8.6+/-3.9 yr, affected by idiopathic isolated GH deficiency (GHD), and in a group of 27 children (15 male, 12 female), age 10.9+/-3.3 yr, with constitutional growth delay. Results showed that basal and peak leptin levels as well as the AUC were significantly higher in GHD patients compared to controls (p<0.05) and correlated with BMI SDS (p<0.0001) in GHD patients. No change in leptin serum levels was observed during either stimulation test. No correlation was found, however, between basal leptin serum levels and basal, peak and the AUC of GH during the tests. Moreover, no correlation was found between the acute changes of serum GH concentration during both stimulation tests and leptin serum levels. The results suggest that leptin and GH secretion is not correlated and that leptin serum levels mainly reflect the amount of fat tissue, which is higher in GHD patients.

The Treadmill Exhausting Test Is Not Suitable for Screening of Growth Hormone Deficiency!

Background/Method: We compared the growth hormone response to a modified exercise test – the treadmill exhausting test – to pharmacological stimulation tests in 77 children with short stature. Each child underwent the treadmill test to individual exhaustion and at least one pharmacological test for GH stimulation. To determine the point of individual exhaustion, the heart rate, workload and oxygen consumption were measured. Results: The mean ± SEM peak GH concentration (ng/ml) in 47 small, normally growing children (group 1) was 16.1 ± 1.3 in the pharmacological tests vs. 5.0 ± 0.6 after a treadmill exhausting test. Thirty children with GH deficiency (group 2) had mean ± SEM peak GH concentrations (ng/ml) of 5.5 ± 0.5 in the pharmacological tests and 4.1 ± 0.7 after physical exercise. The groups differed significantly in the pharmacological tests (p < 0.001) but not in the exhausting test. We found a 90% sensitivity but only a 11% specificity for the treadmill exhausting test compared to the diagnosis obtained by pharmacological testing. Conclusion: We do not recommend the treadmill exhausting test in clinical practice of pediatric endocrinology at all.

Late hormonal complications after brain tumor treatment in childhood and adolescence: literature review and a model of integrated hormone aftercare

The variety of endocrine late-effects after brain tumour therapy in childhood is well known. Growth is usually impaired first due to a hypothalamo-pituitary growth hormone (GH) deficiency or a radiation-induced neurosecretory dysfunction of GH secretion. Generally, all hypothalamo-pituitary axes can be affected. Disturbances of puberty, gonadal function, thyroid function and adrenal function can manifest after a long posttherapeutic interval. A retrospective analysis of the auxological and endocrinological data assessed within the German brain tumour study HIT 91 showed that endocrinological follow-up of these patients was not satisfactory. Therefore we have developed a concept for the new brain tumour study: auxological and laboratory parameters will be assessed before oncological therapy and in regular intervals (4, 12, 18, 24 months after the end of tumour therapy). 24 months after the end of tumour therapy all hypothalamo-pituitary axes are to be evaluated with pharmacological stimulation tests.

Pharmacological testing for thediagnosis of growth hormone deficiency

Evaluation of growth hormone (GH) secretion using pharmacological GH stimulation tests (GHSTs) remains current practice, although the reliability of GHSTs has been questioned and many pitfalls have been pointed out. We have analysed all the 6,373 GHSTs which led to the initiation of GH therapy in 3,233 children treated in France from 1973 to 1989. Eleven different pharmacological tests were used, and 62 out of the 66 theoretical pairs of tests were used at least once. The most frequent combination of tests was used in 12.7% of patients. Reliability of GH peak measured by comparing the results of two tests in the same patient was poor, as measured by intraclass correlation coefficients (all under 0.8). Multivariate analysis identified several parameters positively or negatively associated with peak plasma GH. We believe that several of these factors (i.e. weight standard deviation score (SDS), genetic target height SDS and nature of the agent) identify biases in the diagnosis of GH deficiency (GHD). In addition, we re-evaluated GH secretion in 208 young adults formerly treated with GH for childhood onset GHD. Peak plasma was superior or equal to 10 ng/ml in 81% of patients with former idiopathic GHD. We conclude that the current use of GHSTs as well as the criteria for idiopathic childhood GHD should be questioned.

Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a population register-based study.

Evaluation of GH secretion using pharmacological GH stimulation tests (GHST) remains a current practice, although the reliability of GHST has been questioned, and many pitfalls have been pointed out. We have analyzed all of the 6373 GH stimulation tests that led to the initiation of GH therapy in 3233 children treated in France from 1973-1989. Tests and GH measurements were performed by individual centers and collected by the Association France-Hypophyse. GH deficiency (GHD) was due to craniospinal irradiation (11%), was due to organic causes or associated with multiple deficiencies (22%), or was considered idiopathic (65%); 2% of the patients were considered non-GHD. Eleven different pharmacological tests were used, and 62 of the 66 theoretical pairs of tests were used at least once. The most frequent combination of tests (ornithine in one instance and insulin in another) was used in 12.7% of patients. The reliability of the GH peak measured by comparing the results of 2 tests in the same patient was poor, as measured by intraclass correlation coefficients below 0.8. Multivariate analysis identified several parameters positively or negatively associated with peak plasma GH: calendar year of initiation of treatment, etiology of GHD, height SD score, bone age SD score, puberty, weight SD score, genetic target height SD score, and the nature of the pharmacological agent used. We believe that several of these factors (weight SD score, genetic target height SD score, and nature of the agent) identify biases in the diagnosis of GHD. We conclude that GHST should be performed with a very limited number of agents, interpreted after the establishment of reference values in age-matched normal children, and associated with other clinical and biochemical parameters for establishing the diagnosis of GHD.

Behavior of growth hormone after stimulation with growth hormone releasing hormone (GHRH) in children with disorders of the hypothalamo-hypophyseal axis and girls with Turner syndrome

To investigate the hypothalamic pituitary axis in children with various growth disorders stimulation tests with growth hormone releasing hormone (GHRH) were performed and compared to pharmacological stimulation tests. 103 subjects were studied-15 healthy volunteers, 20 patients with isolated growth hormone deficiency (IGHD), 16 patients with multiple pituitary hormone deficiency (MPHD), 17 children with organic growth hormone deficiency (OGHD) and 35 Turner patients. 1 microgram/kg GHRH was administered iv, blood samples were drawn before GHRH and after 5, 15, 30, 45, 60 and 90 minutes. In 53 patients a second GHRH-test was done after repeated GHRH injections (7 times 1 microgram/kg GHRH every 3 hours). In the group of healthy probands we found wide variations of stimulated growth hormone (GH) levels. In 7 of the 20 patients with IGHD the stimulated GH level exceeded 10 ng/ml in one of the two GHRH-tests. The maximal GH response to the second GHRH-test (8.3 +/- 6.8 ng/ml) was significantly higher (p < or = 0.025) than after the first GHRH-test (5.0 +/- 4.0 ng/ml). In patients with MPHD stimulated GH values were significantly lower than in patients with IGHD (p < or = 0.005). GHRH stimulation tests in OWHM patients did not differ from the results in children with IGHD. The GHRH induced GH response in girls with Turner syndrome was significantly lower than in the healthy volunteers (p < or = 0.025). Basal (p < or = 0.05) and GHRH stimulated GH levels (p < 0.02) were lower after estrogen administration. Pituitary GH secretion could be activated by repeated stimulation with GHRH (priming) in children with hypothalamic GH deficiency. Only in the patients with MPHD a correlation could be found between the result of the GHRH-stimulation and one pharmacological GH test. In children with OGHD the radiation dose was negatively correlated to the maximal GH concentrations after L-Dopa stimulation. Basal and GHRH stimulated GH levels in Turner syndrome were lower after estrogen administration.

Final Height in Turner Syndrome Patients Treated with Growth Hormone

The first treatment trials on patients presenting with Turner syndrome were successful in accelerating growth velocity. It is therefore essential to know the final height of the patients who were treated in order to ascertain whether or not growth hormone treatment increases final height. We are reporting on a group of 117 patients with Turner syndrome whose growth hormone treatment was initiated in 1986. The mean growth hormone dose was 0.74 IU/kg/week for an average period of 4 years. At the start of treatment, the patients' chronological age was 129/12 years, height -3.8 +/- 1.0 standard deviation scores (SDS) and bone age 10.5 +/- 2.1 years. Mean final height was 147.7 +/- 5.6 cm, i.e. a gain of 1.5 SDS. We noted no significant difference due to the type of chromosomal abnormality, nor to oxandrolone or estrogen-associated treatment. A significant correlation was found between final height, mean parental height, the duration of the treatment, height SDS at the start of treatment and growth hormone peak during pharmacological stimulation tests. However, there was no correlation between growth hormone dosage, chronological age and bone age at the start of treatment. These results show that the growth hormone treatment improves the final heights of patients with Turner syndrome.

X-linked agammaglobulinemia, growth hormone deficiency and delay of growth and puberty.

Coinheritance of X-linked agammaglobulinemia and growth hormone deficiency (XLA/GHD) has been classified as an independent primary immune deficiency. We evaluated the pattern of growth and endocrine function in seven XLA subjects (ages 10.9-20.1 years); four belonged to two different XLA pedigrees and three represented sporadic XLA cases. Three had reached adulthood (final stature 176.0, 173.5 and 165.0 cm, respectively) and their retrospective growth showed delay in growth and puberty during adolescence. In the other four subjects, growth hormone production was measured by growth hormone pharmacological stimulation tests (clonidine, arginine): three of four patients had insufficient growth hormone responses (peak growth hormone < 10 micrograms/l); all three had delayed puberty; their growth hormone responses increased after "priming" with testosterone, reaching values > 10 micrograms/l in two of them and allowing diagnosis of "true" growth hormone deficiency in the third. The fourth was a normally growing subject who showed a normal growth hormone response both before and after testosterone priming. Six out of the seven subjects showed a growth pattern consistent with delay in growth and puberty. Our results suggest that true XLA/GHD is rarer than previously supposed and that subnormal responses to growth hormone stimulation tests may be found without sex steroid priming of the test in adolescence. The most probable growth pattern in XLA appears to be delay in growth and puberty, as has already been described for other chronic diseases.

PLASMA ICFI AND IGF-BP3 LFVELS AS DIAGNOSIS CRITERIA OF GH DEFICIENCY

Idiopathic GH deficiency (GHD) is a clinically and biologically heterogeneous condition, making it difficult to diagnose. We have shown that the magnetic resonance imaging (MRI) aspect (Argyropoulon, J pediatr 1992, p.886) and the growth response during the first 2 yrs of hGH therapy are good criteria of GHD. Forty nine patients with height of ←2SD and a GH peak response after 2 pharmacological stimulation tests of < 10 ng/ml were classified according to the accuracy of the diagnosis of GHD: Group I (n=22) certain GHD with pituitary stall interruption or familial form;m Group II (n=14) without these criteria; Group III (n=13) tranisient GHD with GH peak ≥ 10 ng/ml after a 3rd provocative test performed after a 15-d interruption of hGH therapy. In groups II and III pituitary height on MRI was normal in 9,←2SD in 6 and not evaluated in 12 patients. Other causes of short stature were excluded. IGFI was measured in the plasma without extraction by the non-equilibrium technic described by Furlanetto and al. and IGF-BP3 by a RIA (DSL., Webster, Texas). The results were compared to those found in prepubertal idiopathic short childre : lowest limits were 0.2u/ml and 2 μg/ml for IGFI and IGF-BP3 respectively (m±SE : 0.8±0.1 u/ml and 4±10 1 μ/ml). GH peak, IGFI and IGF-BP3 were lower(p<0.001) in I than in II and III. In Group I, these 3 parameters were not modified by associated thyrotropin deficiency (10 cases) or spontateous hypoglycemia (9 cases). Conclusion. Almost all patients with certain GHD had low values of IGFI and IGF-BP3. Conversely those with transient form and /or normal pituitary anatomy had normal values. Pituitary stalk interruption, height increase ≥ ISD during the 1st years of hGH therapy, IGFI<0.2u/ml, and IGF-BP3<2μg/ml are markers of the diagnosis of GHD. When these criteria are absebt or disordant further evaluation is necessary. (supported by a grant from Assistance Publique-Hopitaux de paris.)

Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed weighting index

A total of 5473 pharmacological stimulation tests were carried out in 3143 children and subjected to statistical analysis. The mean chronological age of the children was 9 years 9 months (range 3 years to 16 years 6 months) and mean bone age was 7 years 6 months (range 2 years to 14 years). Nine pharmacological tests were used: (1) arginine (n = 625); (2) clonidine (n = 339); (3) insulin (n = 198); (4) ornithine (n = 162); (5) insulin and arginine (n = 203); (6) clonidine and betaxolol (n = 2003); (7) L-dopa (n = 685); (8) glucagon and propranolol (n = 443); and (9) glucagon and betaxolol (n = 815). Measurement of plasma growth hormone was always performed using the same method. The distribution of values in each test was of the gausso-logarithmic type. The results of the mean peak and the 95% confidence limit were as follows: (1) 10.2, 0.45; (2) 11.5, 0.7; (3) 11.8, 0.8; (4) 14.2, 1.2; (5) 14.3, 0.9; (6) 15.7, 1.1; (7) 19.8, 2.1; (8) 20.8, 2.3; (9) 21, 2.5. These results lead to the following conclusions: the specificity of these tests is low, the mean peak may vary two-fold from one test to another, and the percentage of peaks < 10 ng/ml ranges from 69% for test 1 to 29% for tests 8 and 9. The proportion of growth hormone deficiencies thus varies considerably according to the test used.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth Response to Growth Hormone during the First Year as a Diagnosis Criterion of Growth Hormone Deficiency

Idiopathic growth hormone (GH) deficiency is a clinically and biologically heterogeneous condition. This study evaluates the capacity of the initial growth response to hGH therapy to distinguish certain from transient GH deficiency. Twenty-five patients having a GH peak < 10 micrograms/l after 2 pharmacological stimulation tests were classified according to the accuracy of the diagnosis of GH deficiency. Group 1 (n = 17) had certain GH deficiency because of pituitary stalk interruption syndrome and/or familial form. Group 2 (n = 8) had a transient GH deficiency. The mean increase in height standard deviation (SD) was 1.3 +/- 0.1 (mean +/- SE) and 0.5 +/- 0.1 during the first and second years in group 1 and 0.4 +/- 0.1 (p < 0.0005, compared to group 1) and 0.1 +/- 0.2 (p < 0.025 compared to group 1) during the first and second years in group 2. During the first year of therapy, the increase in height was > or = 1 SD in 14 patients of group 1 and in 1 patient of group 2. In group 1, this increase was positively correlated with an increase in body mass index (r = 0.80, p < 0.01) during the first year and with target height (r = 0.60, p < 0.02) during the second year. Growth rate (SD for age) during the first year in this group was negatively correlated with the height prior to therapy (r = -0.72, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal stimulation tests

Both pharmacological and mechanical stimulation tests are used to evaluate the motor function of the esophagus and its sphincters. The stimulation of the esophagus allows not only evaluation of basal motor parameters but gives also information about the capability of the organ to respond to defined stimuli. Pentagastrin and edrophonium have been used to stimulate the esophageal motor function mainly with the intension of revealing abnormal motility patterns. In the esophageal body, the administration of the compounds allows detection of motor abnormalities. In contrast to a pharmacological stimulation test, the response of the lower esophageal sphincter to mechanical stimulation with an increase in abdominal pressure-applied by leg raising or using an abdominal beltremains a controversials field. The conflict is due to the fact that some investigators postulate an atropine-sensitive or vagally mediated reflex, whereas others suggest a purely mechanical extrinsic compression of the intraabdominal portion of the esophagus. The latter explanation seems to be wrong due to the fact that during mechanical stimulation with “intermittend abdominal compression” the change in pressure in the LES exceeds the time of the mechanical stimulation. The results were obtained in healthy persons and in patients with different esophageal motility disorders. It was concluded, therefore, that an increase in abdominal pressure results in an adaptive pressure rise in the LES, which can be used to evaluate the lower esophageal sphincter in a more detailed and functional way. In the esophageal body abnormal motility patterns can be more distinctly provoked by inducing swallowing with a defined bolus. Wet swallows more frequently allow detection of esophageal motor dysfunction than dry swallows. The inflation of a balloon in the esophageal body is sometimes helpful in patients with noncardiac chest pain to correlate mechanical stress with esophageal related symptoms.