A Review of Growth Hormone Stimulation Tests in Children

PEDIATRICS ◽  
1974 ◽  
Vol 53 (6) ◽  
pp. 929-937
Author(s):  
S. Douglas Frasier
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Current Evidence ◽  
Oral Glucose ◽  
Normal Children ◽  
Small Magnitude ◽  
Arginine Infusion ◽  
Sequential Administration ◽  
Stimulation Tests

No suggested screening test meets all of the criteria set for such a procedure. The minimum incidence of a positive response in normal children detected in a single blood sample after diethylstilbestrol, sleep or exercise is approximately 70%. This is higher than that observed when a single sample is obtained following oral glucose. While both sleep and exercise are physiologic stimuli, the former may be quite inconvenient unless an outpatient facility staffed with appropriate personnel is available. An exercise test employed in the office may well be the best screening procedure for the practicing physician. The optimal criteria for a definitive test of growth hormone function are also not met by any single stimulus. Insulin-induced hypoglycemia, arginine infusion, intramuscular glucagon and oral 1-DOPA are all useful procedures. None alone discriminate completely between the normal and the growth hormone-deficient child. Despite potential hazards, insulin-induced hypoglycemia remains the standard against which other stimuli are judged. Arginine and 1-DOPA appear to be equally effective. The literature contains insufficient data to allow adequate evaluation of intramuscular glucagon alone, and the results of combined propranolol-glucagon stimulation, while promising, require confirmation. Because of an inconstant and/or small magnitude of response leading to results which are difficult to interpret, the use of glucose, pyrogen, vasopressin and ACTH are not adequate tests of growth hormone function. Bovril® is a satisfactory stimulus for those children who will take it. Those factors which modify the growth hormone response must be considered in evaluating the results of stimulation tests. Blunted responses should be interpreted with extreme caution in the obese child. A fasting growth hormone concentration ≥ 7 ng/ml is presumptive evidence of intact growth hormone function regardless of the subsequent response to stimulation. It is essential that patients be euthyroid in order to interpret the results of growth hormone function tests. Physiologic glucocorticoid replacement therapy should not confuse the interpretation of results. Whether or not pretreatment with sex steroids is worthwhile in the routine evaluation of children for suspected growth hormone deficiency is an open question. Although it is agreed that the definitive diagnosis of growth hormone deficiency depends on the demonstration of failure to respond to two stimuli, which two are most satisfactory is not settled. The sequential administration of arginine and insulin on the same day appears to limit significantly the incidence of false-positive laboratory diagnoses of growth hormone deficiency. The significance of intermediate values in response to stimulation remains unclear. Caution should be exercised in assigning a child to the category of partial growth hormone deficiency. This question must be answered ultimately by the response to HGH therapy in the individual patient. Finally, several points should be kept in mind. All of the tests described depend on the detection and quantitation of immunologically active HGH and biological activity is not necessarily associated with the material(s) being measured. Since many of the stimuli used in the evaluation of growth hormone function are clearly pharmacologic, the physiological significance of the response to such stimuli must be interpreted with caution. The best current evidence suggests that all of the stimuli described act through an intact hypothalamus and pituitary. Differentiation between hypothalamic and pituitary sites of defective growth hormone function awaits the availability of growth hormone-releasing factor(s).

TYPICAL CASES OF ISOLATED GROWTH HORMONE DEFICIENCY WITH AUTOSOMAL RECESSIVE INHERITANCE

1970 ◽  
Vol 63 (4) ◽  
pp. 618-624 ◽  
Author(s):  
Y. Kumahara ◽  
Y. Okada ◽  
K. Miyai ◽  
H. Iwatsubo
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Adult Subject ◽  
Hormone Deficiency ◽  
Recessive Inheritance ◽  
Arginine Infusion ◽  
Isolated Growth Hormone Deficiency ◽  
Male Dwarf

ABSTRACT A 25-year-old male dwarf and his sister, a 31-year-old woman were investigated. Their respective heights were 114 and 97 cm with proportional statures. Their bone ages were that found in the adult subject. Thyroid functions and metyrapone test were normal and the total urinary gonadotrophin was determined in both cases. HGH secretion was not stimulated by insulin-induced hypoglycaemia, arginine infusion or exercise. Their parents and six other siblings were normal in height. The two patients were therefore assumed to be suffering from an isolated growth hormone deficiency with autosomal recessive inheritance.

GROWTH AND GROWTH HORMONE. IV. LIMITATIONS OF THE GROWTH HORMONE RESPONSE TO INSULIN AND ARGININE AND OF THE IMMUNOREACTIVE INSULIN RESPONSE TO ARGININE IN THE ASSESSMENT OF GROWTH HORMONE DEFICIENCY IN CHILDREN

PEDIATRICS ◽  
1969 ◽  
Vol 43 (6) ◽  
pp. 989-1004
Author(s):  
R. Youlton ◽  
S. L. Kaplan ◽  
M. M. Grumbach
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Insulin Administration ◽  
Arginine Infusion ◽  
Group 3 ◽  
Group 2 ◽  
Serum Gh ◽  
Group 1

The growth hormone (GH) response to insulin-induced hypoglycemia and to arginine infusion has been evaluated in 60 children with growth retardation. These children have been classified into three groups: Group 1-9 children had peak serum growth hormone values of 7 mµg/ml or greater to both stimuli, a normal growth hormone response. Group 2-18 children had peak GH values of ≤ 3 mµg/ml to both stimuli, an abnormal response indicating growth hormone deficiency. Group 3-6 children had a blunted GH response (> 3 < 7 mµg/ml) to both stimuli; 8 showed a normal rise in serum GH following arginine infusion (> 7 mµg/ml) but exhibited no rise, or a minimal one, following insulin administration; 9 children had minimal increase in serum GH concentration following arginine infusion but showed a normal GH response to insulin administration (> 7mµg/ml). Children included in Group 3 represent a heterogenous population. In some patients with a blunted response to both stimuli, evidence of partial or less severe form of GH deficiency was found, whereas in 17 of 18 children exhibiting a disparate response the impaired growth was not attributable to growth hormone deficiency. The blood glucose at all sampling periods was significantly lower following insulin administration in patients in Group 2 than that observed for children in Group 1 and 3. The blood glucose was significantly lower at 90 and 120 minutes following arginine infusion in Group 2 compared to values for patients in Group 1 and 3. Changes in serum insulin in response to the infusion of arginine did not provide a useful index of discrimination among these groups. Administration of diethylstilbestrol, 10 mg/day times 2 days, prior to testing can modify the GH response to both hypoglycemia and arginine; it is a useful ancillary procedure in children with blunted or disparate responses. These studies suggest that two types of stimulation tests are necessary to establish the diagnosis of isolated GH deficiency with a high degree of probability.

scholarly journals Isolated growth hormone deficiency presenting with recurrent hypoglycaemia in a toddler

2019 ◽  
Vol 12 (7) ◽  
pp. e231056
Author(s):  
Hiya Boro ◽  
Alpesh Goyal ◽  
Rajesh Khadgawat
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Laboratory Evaluation ◽  
Age Group ◽  
Metabolic Defects ◽  
Stimulation Tests ◽  
Work Up ◽  
Detailed Work ◽  
In Infants And Children

Hypoglycaemia in infants and children is caused by a number of endocrine and metabolic defects, some of which are unique to this age group. Growth hormone deficiency (GHD) has been rarely reported as a cause of recurrent fasting hypoglycaemia in children. An 18-month-old male child presented to us for evaluation of neuroglycopenic symptoms caused by recurrent episodes of fasting hypoglycaemia. Laboratory evaluation revealed ketotic hypoinsulinaemic hypoglycaemia. The child was diagnosed to have GHD on the basis of two failed stimulation tests. A detailed work-up for metabolic and other hormonal causes of hypoglycaemia was negative. We present the case for its rarity and to highlight the importance of a detailed metabolic and hormonal assessment in evaluation of childhood hypoglycaemia.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF GROWTH HORMONE DEFICIENCY IN ADULTS AND PATIENTS TRANSITIONING FROM PEDIATRIC TO ADULT CARE

2019 ◽  
Vol 25 (11) ◽  
pp. 1191-1232 ◽  
Author(s):  
Kevin C. J. Yuen ◽  
Beverly M. K. Biller ◽  
Sally Radovick ◽  
John D. Carmichael ◽  
Sina Jasim ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
American Association ◽  
Hormone Deficiency ◽  
Insulin Like Growth Factor ◽  
Glucagon Stimulation Test ◽  
Adult Care ◽  
Stimulation Tests ◽  
Long Acting

Objective: The development of these guidelines is sponsored by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPG). Methods: Recommendations are based on diligent reviews of clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols. Results: The Executive Summary of this 2019 updated guideline contains 58 numbered recommendations: 12 are Grade A (21%), 19 are Grade B (33%), 21 are Grade C (36%), and 6 are Grade D (10%). These detailed, evidence-based recommendations allow for nuance-based clinical decision-making that addresses multiple aspects of real-world care of patients. The evidence base presented in the subsequent Appendix provides relevant supporting information for the Executive Summary recommendations. This update contains 357 citations of which 51 (14%) are evidence level (EL) 1 (strong), 168 (47%) are EL 2 (intermediate), 61 (17%) are EL 3 (weak), and 77 (22%) are EL 4 (no clinical evidence). Conclusion: This CPG is a practical tool that practicing endocrinologists and regulatory bodies can refer to regarding the identification, diagnosis, and treatment of adults and patients transitioning from pediatric to adult-care services with growth hormone deficiency (GHD). It provides guidelines on assessment, screening, diagnostic testing, and treatment recommendations for a range of individuals with various causes of adult GHD. The recommendations emphasize the importance of considering testing patients with a reasonable level of clinical suspicion of GHD using appropriate growth hormone (GH) cut-points for various GH–stimulation tests to accurately diagnose adult GHD, and to exercise caution interpreting serum GH and insulin-like growth factor-1 (IGF-1) levels, as various GH and IGF-1 assays are used to support treatment decisions. The intention to treat often requires sound clinical judgment and careful assessment of the benefits and risks specific to each individual patient. Unapproved uses of GH, long-term safety, and the current status of long-acting GH preparations are also discussed in this document. LAY ABSTRACT This updated guideline provides evidence-based recommendations regarding the identification, screening, assessment, diagnosis, and treatment for a range of individuals with various causes of adult growth-hormone deficiency (GHD) and patients with childhood-onset GHD transitioning to adult care. The update summarizes the most current knowledge about the accuracy of available GH–stimulation tests, safety of recombinant human GH (rhGH) replacement, unapproved uses of rhGH related to sports and aging, and new developments such as long-acting GH preparations that use a variety of technologies to prolong GH action. Recommendations offer a framework for physicians to manage patients with GHD effectively during transition to adult care and adulthood. Establishing a correct diagnosis is essential before consideration of replacement therapy with rhGH. Since the diagnosis of GHD in adults can be challenging, GH–stimulation tests are recommended based on individual patient circumstances and use of appropriate GH cut-points. Available GH–stimulation tests are discussed regarding variability, accuracy, reproducibility, safety, and contraindications, among other factors. The regimen for starting and maintaining rhGH treatment now uses individualized dose adjustments, which has improved effectiveness and reduced reported side effects, dependent on age, gender, body mass index, and various other individual characteristics. With careful dosing of rhGH replacement, many features of adult GHD are reversible and side effects of therapy can be minimized. Scientific studies have consistently shown rhGH therapy to be beneficial for adults with GHD, including improvements in body composition and quality of life, and have demonstrated the safety of short- and long-term rhGH replacement. Abbreviations: AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; AHSG = alpha-2-HS-glycoprotein; AO-GHD = adult-onset growth hormone deficiency; ARG = arginine; BEL = best evidence level; BMD = bone mineral density; BMI = body mass index; CI = confidence interval; CO-GHD = childhood-onset growth hormone deficiency; CPG = clinical practice guideline; CRP = C-reactive protein; DM = diabetes mellitus; DXA = dual-energy X-ray absorptiometry; EL = evidence level; FDA = Food and Drug Administration; FD-GST = fixed-dose glucagon stimulation test; GeNeSIS = Genetics and Neuroendocrinology of Short Stature International Study; GH = growth hormone; GHD = growth hormone deficiency; GHRH = growth hormone–releasing hormone; GST = glucagon stimulation test; HDL = high-density lipoprotein; HypoCCS = Hypopituitary Control and Complications Study; IGF-1 = insulin-like growth factor-1; IGFBP = insulin-like growth factor–binding protein; IGHD = isolated growth hormone deficiency; ITT = insulin tolerance test; KIMS = Kabi International Metabolic Surveillance; LAGH = long-acting growth hormone; LDL = low-density lipoprotein; LIF = leukemia inhibitory factor; MPHD = multiple pituitary hormone deficiencies; MRI = magnetic resonance imaging; P-III-NP = procollagen type-III amino-terminal pro-peptide; PHD = pituitary hormone deficiencies; QoL = quality of life; rhGH = recombinant human growth hormone; ROC = receiver operating characteristic; RR = relative risk; SAH = subarachnoid hemorrhage; SDS = standard deviation score; SIR = standardized incidence ratio; SN = secondary neoplasms; T3 = triiodothyronine; TBI = traumatic brain injury; VDBP = vitamin D-binding protein; WADA = World Anti-Doping Agency; WB-GST = weight-based glucagon stimulation test

scholarly journals Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence

2015 ◽  
Vol 101 (1) ◽  
pp. 96-100 ◽  
Author(s):  
P G Murray ◽  
M T Dattani ◽  
P E Clayton
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Childhood And Adolescence ◽  
Supporting Evidence ◽  
Diagnosis And Management ◽  
False Positive Diagnosis ◽  
Starting Dose ◽  
Igf I ◽  
Stimulation Tests

Growth hormone deficiency (GHD) is a rare but important cause of short stature in childhood with a prevalence of 1 in 4000. The diagnosis is currently based on an assessment of auxology along with supporting evidence from biochemical and neuroradiological studies. There are significant controversies in the diagnosis and management of GHD. Growth hormone (GH) stimulation tests continue to play a key role in GHD diagnosis but the measured GH concentration can vary significantly with stimulation test and GH assay used, creating difficulties for diagnostic accuracy. Such issues along with the use of adjunct biochemical markers such as IGF-I and IGFBP-3 for the diagnosis of GHD, will be discussed in this review. Additionally, the treatment of GHD remains a source of much debate; there is no consensus on the best mechanism for determining the starting dose of GH in patients with GHD. Weight and prediction based models will be discussed along with different mechanisms for dose adjustment during treatment (auxology or IGF-I targeting approaches). At the end of growth and childhood treatment, many subjects diagnosed with isolated GHD re-test normal. It is not clear if this represents a form of transient GHD or a false positive diagnosis during childhood. Given the difficulties inherent in the diagnosis of GHD, an early reassessment of the diagnosis in those who respond poorly to GH is to be recommended.

Circulating immunoreactive somatostatin in man. Effect of age, pregnancy, growth hormone deficiency and achlorhydria

1985 ◽  
Vol 110 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Susan M. Webb ◽  
John A. H. Wass ◽  
Erica Penman ◽  
M. Murphy ◽  
José Serrano ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Pernicious Anaemia ◽  
Hormone Deficiency ◽  
Control Group ◽  
Normal Children ◽  
The Third ◽  
Group 12 ◽  
The Mean ◽  
Effect Of Age

Abstract. Plasma immunoreactive somatostatin (IRS) levels were measured fasting at 09.00 h in groups of adult individuals and children of different ages, as well as in pregnant women, in patients with pernicious anaemia documented to be achlorhydric, and in children with growth hormone deficiency. There was a gradual rise in the mean level of IRS from the third decade (mean 35.8 ± 3.8 pg/ml), which reached significance at the seventh (61.1 ± 8.4 pg/ml), eighth (66.7 ± 5 pg/ml) and ninth decade (82.6 ± 13.8 pg/ml). No change was observed in the second 28.3 ± 3.8 pg/ml) and third (31.1 ± 3.2 pg/ml) trimester of pregnancy when compared with matched, non-pregnant controls (29.7 ± 2.2 pg/ml); however, the children aged under 2 years (69.6 ± 11.2 pg/ml) had significantly higher values than the eldest group (12 to 16 years old) (46.3 ± 7.2 pg/ml) (P < 0.05). In achlorhydric patients, basal (27.2 ± 3.7 pg/ml; P < 0.01) and postprandial IRS (42.8 ± 7.7 pg/ml; P < 0.001) was significantly lower than in a matched, normal control group (basal 59.4 ± 7.2; postprandial 132.1 ± 26.3 pg/ml). Growth hormone deficiency was not associated with any differences in circulating IRS, basally or after insulin hypoglycaemia, when compared with values in normal children. These results would suggest, 1) that age has a significant effect on plasma IRS, and should be considered in the interpretation of fasting plasma levels of IRS; 2) that pregnancy and growth hormone deficiency is not accompanied by any changes in circulating IRS and presumably, somatostatin binding proteins; 3) that gastric acid is necessary for a normal release of IRS from the gastrointestinal tract to the circulation.

scholarly journals Reduction in Pediatric Growth Hormone Deficiency and Increase in Central Precocious Puberty Diagnoses During COVID 19 Pandemics

2021 ◽  
Author(s):  
Martina Peinkhofer ◽  
Benedetta Bossini ◽  
Arturo Penco ◽  
Manuela Giangreco ◽  
Maria Chiara Pellegrin ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Retrospective Study ◽  
Growth Hormone Deficiency ◽  
Precocious Puberty ◽  
Screen Time ◽  
Central Precocious Puberty ◽  
Hormone Deficiency ◽  
Tertiary Center ◽  
Stimulation Tests ◽  
Children’S Anxiety

Abstract Objective: The study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics.Methods: Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 e 2020 in a tertiary center.Results: Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (-10% tests; -8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (-35%), while LHRH tests increased (+22%). A reduction of 30% in GHD diagnosis was observed. Diagnosis of central precocious puberty (CPP) increased by 38% compared to 2019, mainly in females. Conclusion: This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children's growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children's anxiety as possible triggers of CPP.

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