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.

The effect of growth hormone on the plasma levels of T4, free-T4, T3, reverse T3 and TBG in hypopituitary patients

1981 ◽  
Vol 96 (4) ◽  
pp. 475-479 ◽  
Author(s):  
G. Gács ◽  
Cs. Bános
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Growth Hormone Treatment ◽  
Plasma Concentrations ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
Slight Reduction ◽  
Reverse T3 ◽  
Group 2 ◽  
Group 1

Abstract. The plasma concentrations of thyroxine (T4), free thyroxine (free-T4), triiodothyronine (T3), reverse triiodothyronine (rT3), TSH and thyroxine-binding globulin (TBG) were measured in 19 children suffering from idiopathic growth hormone deficiency. Blood was taken before and one month after growth hormone treatment. Ten patients were hypothyroid (group 1) and 9 were euthyroid (group 2). The basal T3 and rT3 levels correlated well with the T4 concentrations. Free-T4 levels were very low in all the hypothyroid patients and proved to be the most reliable index of TSH deficiency. TBG concentration was high in the hypopituitary patients regardless of their thyroid function. Following growth hormone treatment T4, free-T4 and rT3 levels fell in both groups. The T3 concentration rose in group 1 but no change was seen in group 2. There was a significant correlation between the changes of T4 and T3, such that the increase in T3 level was greatest in those with only a slight reduction of T4 concentration and no T3 increase was seen with more marked T4 decreases. The plasma TBG concentration is enhanced in growth hormone deficiency causing relatively high T4 values. Growth hormone treatment reduces T4 secretion and affects the peripheral metabolism of thyroid hormones resulting in an increase of T3 and a reduction of rT3 concentration.

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.

scholarly journals Responses of serum GH and somatomedin-C to an analogue of GHRH in children with growth hormone deficiency

1984 ◽  
Vol 18 (11) ◽  
pp. 1206-1206
Author(s):  
A Grossman ◽  
M O Savage ◽  
A Blacklay ◽  
N Lytras ◽  
P N Plowman ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Hormone Deficiency ◽  
Somatomedin C ◽  
Serum Gh

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).

Evolution of growth hormone neurosecretory disturbance after cranial irradiation for childhood brain tumours: a prospective study

1996 ◽  
Vol 150 (2) ◽  
pp. 329-342 ◽  
Author(s):  
H A Spoudeas ◽  
P C Hindmarsh ◽  
D R Matthews ◽  
C G D Brook
Keyword(s):  
Growth Hormone ◽  
Brain Tumours ◽  
Fourier Transforms ◽  
Pulse Amplitude ◽  
Progressive Increase ◽  
Cranial Irradiation ◽  
Partial Recovery ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

Abstract To determine the aetiopathology of post-irradiation growth hormone (GH) deficiency, we performed a mixed longitudinal analysis of 56 24 h serum GH concentration profiles and 45 paired insulin-induced hypoglycaemia tests (ITT) in 35 prepubertal children, aged 1·5–11·8 years, with brain tumours in the posterior fossa (n=25) or cerebral hemispheres (n = 10). Assessments were made before (n = 16), 1 year (n = 25) and 2 to 5 years (n = 15) after a cranial irradiation (DXR) dose of at least 30 Gy. Fourier transforms, occupancy percentage, first-order derivatives (FOD) and mean concentrations were determined from the GH profiles taken after neurosurgery but before radiotherapy (n = 16) and in three treatment groups: Group 1: neurosurgery only without DXR (n = 9); Group 2: ≥30 Gy DXR only (n = 22); Group 3: ≥30 Gy DXR with additional chemotherapy (n = 9). Results were compared with those from 26 short normally growing (SN) children. Compared with SN children, children with brain tumours had faster GH pulse periodicities (200 min vs 140 min) and attenuated peak GH responses to ITT (24·55 (19·50–30·20) vs 8·32 (4·57–15·14) mU/I) after neurosurgery, before radiotherapy. However, spontaneous GH peaks (19·05 (15·49–23·44) vs 14·13 (9·12–21·38) mU/l), 24 h mean GH (5·01 (4·37–5·62) vs 3·98 (2·63–5·89) mU/l) and FODs (1·43 (1·17–1·69) vs 1·22 (0·88–1·56) mU/l per min) were similar. The abnormalities present before radiotherapy persisted in group 1 children at 1 year when 24 h mean GH (2·45 (1·17– 5·01) mU/l) and FODs (0·73 (0·26–1·20) mU/l per min) were additionally suppressed, although partial recovery was evident by 2 years. With time from radiotherapy, there was a progressive increase in GH pulse periodicity (Group 2: 200 min at 1 year, 240 min at ≥2 years; Group 3: 140 min at 1 year, 280 min at ≥2 years) and a decrease in 24 h mean GH (Group 2 vs Group 3 at ≥2 years: 2·45 (1·70–3·47) vs 1·86 (1·32–2·69) mU/l) and FODs (Group 2 vs Group 3 at ≥2 years; 0·56 (0·44–0·69) vs 0·44 (0·27–0·61) mU/l per min). Initial discrepancies between measures of spontaneous and stimulated (ITT) GH peaks were lost by 2 or more years (spontaneous vs ITT; Group 2: 7·76 (5·89–9·77) vs 3·80 (0·91–15·84) mU/l; Group 3: 6·03 (4·27–8·32) vs 3·80 (0·31–46·77) mU/l). After cranial irradiation, a number of changes evolved within the GH axis: faster GH pulse periodicities and discordance between physiological and pharmacological tests of GH secretion before irradiation gave way to a slow GH pulse periodicity, decreased GH pulse amplitude and rate of GH change (FOD) and, with time, eventual concordance between physiological and pharmacological measures. The evolution of these disturbances may well reflect differential pathology affecting hypothalamic GH-releasing hormone and somatostatin. Journal of Endocrinology (1996) 150, 329–342

New approach to the diagnosis of growth hormone deficiency in adults

1996 ◽  
Vol 134 (3) ◽  
pp. 352-356 ◽  
Author(s):  
Ezio Ghigo ◽  
Gianluca Aimaretti ◽  
Laura Gianotti ◽  
Jaele Bellone ◽  
Emanuela Arvat ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
Serum Insulin ◽  
Normal Subjects ◽  
Hormone Deficiency ◽  
New Approach ◽  
Igf I ◽  
Ghrh Test ◽  
Gh Deficiency In Adults

Ghigo E, Aimaretti G, Gianotti L, Bellone J, Arvat E, Camanni F. New approach to the diagnosis of growth hormone deficiency in adults. Eur J Endocrinol 1996;134:352–6. ISSN 0804–4643 Pyridostigmine (PD), a muscarinic cholinergic agonist, and arginine (ARG) clearly increase the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) in man. The current study was undertaken to investigate the value and safety of PD + GHRH and ARG + GHRH tests as well as the measurement of serum insulin-like growth factor I (IGF-I) in diagnosing GH deficiency in adults. Fifty-four patients considered GH deficient from extensive organic or idiopathic pituitary disease and 326 healthy adults were studied. The IGF-I concentrations were lower than the 3rd percentile of normal values in only 31 of the 54 (57.4%) patients with hypopituitarism. However, the IGF-I levels in hypopituitary patients and in normal subjects overlapped more frequently between 41 and 60 years (50%) and between 61 and 80 years (92.3%) as opposed to between 20 and 40 years (8.6%). In contrast to the IGF-I measurement, the ranges of peak GH responses to PD + GHRH and ARG + GHRH tests were clearly differentiated between the hypopituitary (0.2–6.8 and 0.1–9.5 μg/l, respectively) and normal subjects 17.7–114 and 16.1–119 μg/l, respectively). However, the PD + GHRH test was reliable only in subjects of 20–40 years of age. In conclusion, IGF-I measurement had no value in the diagnosis of GH deficiency in adults aged over 40 years, but is reliable enough when young adults of 20–40 years of age are considered. Both PD + GHRH and ARG + GHRH testing should be considered more reliable biochemical measurements of GH deficiency. In contrast to the PD + GHRH test, the ARG + GHRH test is reliable throughout the adult lifespan and appears to be the most appropriate for patient compliance and safety. F Camanni, Divisione di Endocrinologia, Ospedale Molinette, C.so Dogliotti 14, 10126 Torino, Italy

scholarly journals Growth hormone deficiency in adults. Introduction to the problem

1994 ◽  
Vol 40 (4) ◽  
pp. 65-81
Author(s):  
М. Bengt-Ake Bengtsson
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Replacement Therapy ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Control Group ◽  
Objective Criterion ◽  
Double Blind ◽  
Gh Replacement ◽  
Severe Degree

Growth hormone deficiency (GH) for a long time was recognized only in childhood. Compelling evidence has been obtained showing that HR replacement therapy effectively stimulates growth and, in many cases, achieves normal end-points of physical development. More recently, it was shown that the most effective in this regard was the appointment of regular evening injections of the drug, which mimic the physiological secretion of GH during sleep. Despite the fact that the acceleration of linear growth is the most objective criterion for the effectiveness of therapy for GH, it is known that GH has a significant effect on body structure, causing a decrease in fat mass and an increase in muscle mass. Until recently, GH was not considered an important hormonal regulator in adults, and therefore, there was no study of GH deficiency and treatment of children with GH deficiency when they reached adulthood, as well as patients with hypopituitarism who became ill in adulthood. However, in 1989, as a result of two double-blind trials using placebo in the control group, the effectiveness of GH replacement therapy in adults with an abnormally low level of GH, up to a severe degree of GH deficiency, was revealed. Further studies showed the presence of violations of both physical and mental status in adults in whom GH deficiency develops as a result of the tumor process in the pituitary gland or its therapy. Most of these disorders, but not all, can be corrected as a result of GH replacement therapy, which confirms the significant effect of GH throughout life.

scholarly journals Partial Loss of Function of the GHRH Receptor Leads to Mild Growth Hormone Deficiency

2016 ◽  
Vol 101 (10) ◽  
pp. 3608-3615 ◽  
Author(s):  
Louise Cheryl Gregory ◽  
Kyriaki Sandy Alatzoglou ◽  
Mark James McCabe ◽  
Peter Christopher Hindmarsh ◽  
Jose William Saldanha ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
Final Height ◽  
Fold Increase ◽  
Hormone Deficiency ◽  
Loss Of Function ◽  
Partial Loss ◽  
Mild Phenotype ◽  
Partial Activity

Objective: Recessive mutations in GHRHR are associated with severe isolated growth hormone deficiency (IGHD), with a final height in untreated patients of 130 cm ± 10 cm (−7.2 ± 1.6 SDS; males) and 114 ± 0.7 cm (−8.3 ± 0.1 SDS; females). Design: We hypothesized that a consanguineous Pakistani family with IGHD in three siblings (two males, one female) would have mutations in GH1 or GHRHR. Results: Two novel homozygous missense variants [c.11G>A (p.R4Q), c.236C>T (p.P79L)] at conserved residues were identified in all three siblings. Both were absent from control databases, aside from pR4Q appearing once in heterozygous form in the Exome Aggregation Consortium Browser. The brothers were diagnosed with GH deficiency at 9.8 and 6.0 years (height SDS: −2.24 and −1.23, respectively), with a peak GH of 2.9 μg/liter with low IGF-1/IGF binding protein 3. Their sister presented at 16 years with classic GH deficiency (peak GH <0.1 μg/liter, IGF-1 <3.3 mmol/liter) and attained an untreated near-adult height of 144 cm (−3.0 SDS); the tallest untreated patient with GHRHR mutations reported. An unrelated Pakistani female IGHD patient was also compound homozygous. All patients had a small anterior pituitary on magnetic resonance imaging. Functional analysis revealed a 50% reduction in maximal cAMP response to stimulation with GHRH by the p.R4Q/p.P79L double mutant receptor, with a 100-fold increase in EC50. Conclusion: We report the first coexistence of two novel compound homozygous GHRHR variants in two unrelated pedigrees associated with a partial loss of function. Surprisingly, the patients have a relatively mild IGHD phenotype. Analysis revealed that the pP79L mutation is associated with the compromise in function, with the residual partial activity explaining the mild phenotype.

Quadriceps and hand-grip strength in adults with childhood-onset growth hormone deficiency

1995 ◽  
Vol 132 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Alessandro Sartorio ◽  
Marco Narici ◽  
Antonio Conti ◽  
Marco Monzani ◽  
Giovanni Faglia
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Grip Strength ◽  
Gh Deficiency ◽  
Vertical Jump ◽  
Body Height ◽  
Hormone Deficiency ◽  
Childhood Onset ◽  
Hand Grip ◽  
Muscle Groups

Sartorio A, Narici M, Conti A, Monzani M, Faglia G. Quadriceps and hand-grip strength in adults with childhood-onset growth hormone deficiency. Eur J Endocrinol 1995;132:37–41. ISSN 0804–4643 The effects of chronic growth hormone (GH) deficiency on muscle size and strength of postural (quadriceps) and non-postural (hand-grip) muscle groups, as well as on vertical jump capacity, were evaluated in six adults with childhood-onset GH deficiency. Data obtained were compared to those recorded in an age-, sex- and exercise-matched healthy control group. Thigh muscle plus bone cross-sectional area (CSAM+B) of the dominant quadriceps was significantly lower (p < 0.001) than in controls, while the CSAM+B/Body height)2 ratio was similar to that of controls. The maximum voluntary contraction (MVC) of the quadriceps of patients was significantly lower (p < 0.002) than in controls, while no differences existed in the quadriceps force expressed per unit area (MVC/CSA) between patients and controls. As far as hand-grip was concerned, the CSAM+B of the dominant forearm was significantly lower (p < 0.003) than in controls, while the CSAM+B/Body height)2 ratio was no different. The hand-grip MVC of patients was significantly lower (p < 0.004) than in controls, while no differences existed in the MVC/CSA ratio. It is noteworthy also that no difference existed in the hand-grip to quadriceps MVC ratio of the two groups. Furthermore, no differences were found in the vertical jump capacity, because both Δ Height and Δ Height/Body weight of patients were not significantly different from those of controls. In conclusion, our study suggests that GH deficiency seems to reduce the size and strength of postural and non-postural muscle groups to the same extent. However, these findings are likely to be attributed to a simple dimensional scaling, because their CSA/ (Body height)2, MVC/CSA and vertical jump capacity were comparable to those of controls. Alessandro Sartorio, Laboratorio Sperimentale di Ricerche Endocrinologiche, Centro Auxologico Italiano, IRCCS, via Ariosto 13, 1-20145 Milan, Italy

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