Peak Growth Hormone Values Research Articles

Comparison of growth hormone responses to growth hormone-releasing factor and clonidine* in women with normal or poor ovarian response to gonadotropin stimulation

To assess the reliability of growth hormone (GH) secretion tests using provocative agents in women of different ovarian status. Comparison of GH secretion in response to clonidine (Catapressan; Boehringer Ingelheim, Reims, France) and growth hormone-releasing factor (GH-RF). University Hospital, Hôpital Tenon, Paris, France. Women categorized as "normal" (n = 6) or "poor" responder (n = 7) to ovarian stimulation with gonadotropins, depending on the follicular development attained at previous IVF attempts. Clonidine (0.300 mg administered orally) once and GH-RF (1 micrograms/kg IV) repeated twice. The tests were performed in random order in each individual on following cycles. Basal and peak GH values, area under the curve (AUC). Poor responder patients show significantly higher basal levels of FSH, GH, and insulin-like growth factor 1; FSH and basal GH levels are positively correlated. Peak GH levels and AUC are not significantly different in both categories of patients, whether GH-releasing factor or clonidine are used as provocative agents. True positive rate is 56.4% at the cutoff value of 7 micrograms/L, with no significant difference between the patients of the normally or poorly responding groups. At the 10-micrograms/L cutoff level, the true positive rate is almost half in the poor responder group (19.0% versus 38.9%), but the difference is not significant. These results raise concern about using the GH secretory response to a single clonidine administration as a predictive test of the therapeutic benefit that could be obtained by co-stimulating the somatotropic axis during a treatment with gonadotropins in poor responder patients, especially when their FSH basal levels are elevated.

Effects of metoclopramide on the growth hormone response to galanin in normal man.

One of the most prominent metabolic effects of the systemic administration of the synthetic neuropeptide galanin in man is the increase in growth hormone (GH) secretion. This stimulating action of galanin is thought to occur directly at the hypothalamic level through the release of GHRH. Recently, it has been shown that also dopaminergic drugs may elicit GH secretion through an increase in hypothalamic GHRH secretion. The aim of this study was to investigate if the action of galanin on GHRH and consequently on GH release may be mediated via dopaminergic pathways evaluating the effects of a potent central dopaminergic receptor blocker, metoclopramide (MCP), on the galanin-induced growth hormone (GH) secretion in normal subjects. We studied seven young non obese healthy subjects (three females and four males). GH secretion was evaluated after 45 min iv infusion of porcine galanin (0.5 mg in 100 ml of saline) from 0 to 45 min combined with a 60 min iv infusion of a) saline (100 ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. In all the seven subjects, during galanin infusion, GH values increased with respect to baseline with peaks occurring between 30 and 60 min after the beginning of galanin infusion. Peak GH values ranged between 3.5 and 15.4 micrograms/l (mean 10.4 +/- 1.6 micrograms/l). During MCP infusion no significant differences in the GH response to galanin with respect to saline were observed both when absolute GH levels and GH AUC were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal GH secretion in liver cirrhosis: evaluation of using GRF test and TRH test.

To evaluate abnormal secretion of growth hormone (GH) in cases of liver diseases, the authors performed a loading test of growth hormone-releasing factor (GRF) and approximately one week later, a loading test of thyrotropin-releasing hormone (TRH), and measured serum GH in 15 cases of liver cirrhosis (LC), 5 with chronic active hepatitis (CAH), and 5 controls. In the TRH test, 8 of 15 LC patients showed a peak GH value of 6 ng/ml or more and were classified as the TRH-responder group (LC-R). Seven other LC patients showing a peak GH value of less than 6 ng/ml were classified as the TRH-non-responder group (LC-NR). None of the CAH cases or controls showed a peak GH value of 6 ng/ml or more. In GRF test, the response of GH was poor in all 8 in the LC-R group. The responses in the LC-NR group were significantly greater than those in the LC-R group from 15 to 90 minutes after the GRF loading. In the LC-R group, greater impairment of liver function was indicated by total bilirubin, serum protein and cholinesterase values compared to the LC-NR group. Fischer's ratio was significantly lower in the LC-R group. In cases of liver diseases, Fischer's ratios negatively correlated with the peak GH values in the TRH test (r = -0.679, P less than 0.01). These results suggest that in LC cases showing a paradoxical GH response to TRH, the GH response to GRF which is a GH stimulatory hormone, is decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Stimulated growth hormone (GH) secretion in children with delays in pubertal development before and after the onset of puberty: relationship with peripheral plasma GH-releasing hormone and somatostatin levels.

A reduced GH secretion has often been shown in prepubertal children with delays in pubertal development. In order to study the mechanism underlying this finding, we evaluated peripheral circulating levels of GH, GHRH, and somatostatin (SRIH) before and after the onset of sexual development in a group of eight late maturing children (six boys, two girls), comparing the results with those obtained in two groups of five prepubertal and four pubertal short children with familial short stature. GH was measured by a two-site immunoradiometric assay. Both GHRH and SRIH were assayed by specific RIAs after an acetone-petrolether extraction from plasma. Our data showed a significant increase (P less than 0.001) in GH, GHRH, and SRIH levels (peak vs. basal values) in response to L-dopa administration in all groups. In pubertal children with delays in pubertal development GH and GHRH peak values (15.8 +/- 2.2 micrograms/L and 120 +/- 18 pg/mL, respectively) were significantly greater (P less than 0.001) than in the same subjects before puberty (8.2 +/- 0.9 micrograms/L and 79 +/- 9 pg/mL, respectively), whereas SRIH peak values did not significantly change (41 +/- 6 vs. 41 +/- 5 pg/mL; P = NS). Furthermore, prepubertal subjects with delays in pubertal development showed GH and GHRH peak values lower (P less than 0.001) than those of prepubertal subjects with FSS (13.3 +/- 1.8 micrograms/L and 120 +/- 13 pg/mL, respectively), whereas no statistical difference was present between the two groups of subjects after pubertal development (18.2 +/- 2.9 micrograms/L and 128 +/- 11 pg/mL, respectively). In conclusion, these findings support the assumption that in late maturing subjects during prepubertal period the decreased GH secretion may be ascribed to a reduced GHRH secretion, reversible with the onset of puberty, without change in circulating SRIH levels.

Growth hormone response to acute growth hormone releasing hormone administration in uraemic patients on haemodialysis.

To examine the response of growth hormone (GH) to growth hormone releasing factor (GHRF) in patients on haemodialysis, we performed the acute GHRF test (50 micrograms administered intravenously as a bolus) in 10 uraemic male patients on haemodialysis and eight normal controls. Each patient was tested before and after a haemodialysis session (at 08.30 and 12.30). Controls were tested on the same time schedule. At 08.30, patients had significantly greater basal and peak GH values (2.5 +/- 0.6 and 27.8 +/- 5.5 micrograms/l) than controls (0.68 +/- and 11.5 +/- 4 micrograms/l). After the haemodialysis session, basal and peak values declined significantly (P less than 0.01) in the uraemic group (0.5 +/- 0.03 and 3.1 +/- 1.1 micrograms/l), whereas the controls did not show such a change in the 12.30 test. Basal and intratest glycaemic values were comparable both before and after haemodialysis. After dialysis test results did not change either with the use of glucose-free dialysate or with bicarbonate buffer. Uraemic patients display a greater GH response to GHRF injection than normal subjects, and this response decreases after haemodialysis. The degree of reduction has no relationship with either glycaemia or the dialysate buffer. We suggest that other GH secretion regulating factors are altered by the haemodialysis procedure.

Effects of dexamethasone on growth hormone (GH)-releasing hormone, arginine- and dopaminergic stimulated GH secretion, and total plasma insulin-like growth factor-I concentrations in normal male volunteers.

In man, glucocorticoid treatment and endogenous corticosteroid excess generally suppress stimulated GH release. However, such effects are not entirely consistent and depend on both the duration of pituitary exposure to steroids and the secretagogue employed. To further evaluate the effects of glucocorticoids in man, we have studied the response to four different GH stimulation tests before and after treatment with dexamethasone (DEX; 2 mg twice daily during 84 h). Twelve healthy male volunteers were divided into two groups of six subjects (groups A and B). Group A underwent stimulation tests with arginine (500 mg/kg, i.v.) and GH-releasing hormone (GHRH, 100 micrograms, i.v.) before and after DEX treatment. Group B were subjected to stimulation tests with two dopaminergic agents, a novel nonergot D2-dopamine agonist CV205-502 (CV; 10 micrograms, i.v.) and dopamine (4 micrograms/kg.min, i.v.), before and after DEX. Within each group, the effect of DEX on the different secretagogues was studied 4 weeks apart. GHRH-stimulated GH release was significantly blunted by DEX treatment [median peak GH value, 34.2 micrograms/L; 25-75th percentiles, 22.1-56.2), control, vs. 19.8 (9.7-34.5), DEX; P less than 0.05; integrated GH secretion expressed as the area under the curve (AUC) was 48% lower after DEX; P less than 0.01]. In the same group, DEX treatment significantly enhanced the response to arginine [10.6 (8.0-22.8), control, vs 26.1 (15.1-38.6), DEX; P less than 0.01; with an increase in AUC of 72%; P less than 0.01]. In group B, under control conditions before glucocorticoid administration, the GH response to CV was significantly greater than that to dopamine in terms of both peak response [25.1 (8.6-30.9), CV, vs. 11.8 (5.5-16.4), dopamine; P less than 0.05] and AUC [2406 +/- 654 (CV) vs. 658 +/- 125 (dopamine); P less than 0.01], suggesting that CV may be a useful adjunct in the diagnosis of GH deficiency. After DEX administration, responses to both dopaminergic agents were suppressed [CV, 6.7 (4.0-21.2); P less than 0.01 vs. control response; and dopamine, 5.3 (4.8-7.9); P less than 0.05 vs. control response]. When compared with the effects of dexamethasone on the GH response to arginine, the results with dopaminergic agents highlight important differences in the mechanisms of action of these indirectly acting GH secretagogues. Moreover, this may be of physiological importance, because in contrast to the inhibitory effect of glucocorticoid on GHRH-stimulated GH release, DEX treatment significantly increased basal plasma GH levels [1.4 (0.5-5.1) vs. control 0.3 (0.1-0.6) microgram/L; P less than 0.001].(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical Utility of Cycle Exercise for the Physiologic Assessment of Growth Hormone Release in Children

The clinical utility of exercise as a stimulus for the physiologic assessment of growth hormone (GH) deficiency was examined in healthy children. In response to exercise tests performed on different days, serum GH concentrations exceeded 7 micrograms/L on both days in 9 of 10 children. Although there is variation in this method of physiologic testing in the response of serum GH concentration (significant mean differences in GH peak values, 27.1 vs 19.8 micrograms/L for the two tests), the exercise test proved clinically valid in that diagnostic levels of GH were exceeded on both days 90% of the time. We conclude that this exercise evaluation protocol has clinical utility for the assessment of GH deficiency in children.

Diagnostic value of insulin-like growth factor-I in short stature.

For the present, to determine growth hormone(GH) deficiency in patients with short stature, many provocative tests using various pharmacological agents such as glucagon, insulin, clonidine, arginine, growth hormone releasing factor, etc. should be done. These are not only complicated but are also misleading in some patients. In search of a simple and accurate method of detecting GH deficiency that may replace the more complicated provocative tests, we measured basal plasma insulin-like growth factor-I (IGF-I) to see the correlation with the peak GH values in the GH stimulation test. But, in each group of patients with different types of short stature, IGF-I values were poorly correlated. In addition, IGF-I values of the patients with short stature compared to the age- and sex-matched normal ranges showed a significant overlap, and the difference between the proportion of patients with subnormal values in GH deficient patients and non-GH deficient patients was not prominent. Nevertheless, in response to human growth hormone (hGH) administration, both the yearly growth rate and IGF-I levels increased conspicuously. Therefore, even though it may not be feasible to use IGF-I as a single diagnostic measure of patients with short stature, the change in IGF-I values in the follow up of hGH therapy may well represent the response to hGH.

79 Growth hormone (GH) response to growth hormone releasing factor (GRF) in Turner Syndrome

Growth hormone deficiency has been described in association with Turner Syndrome, but its mechanisms are unknown.Seventeen prepubertal girls with Turner Syndrome (age 6 5/12 to 15 8/12 years; height - 5,4 to-1,8 SD; weight 93% to 169% of ideal body weight - IBW -) underwent a stimulation test with GRF (0,5 mcg/kg). Plasma GH was measured by radioimmunoassay from - 30 to + 120 minutes. These responses were compared to those we previously reported in children with constitutional short stature - controls - (Hormone Res. 22 : 32, 1985).Peak Plasma GH after GRF was 17,0 ± 3,6 ng/ml (mean ± SEM), significantly lower (p < 0,001) than in control children (39,2 ± 5,1 ng/ml). In Turner patients, peak GH value was negatively correlated with the % of IBW (r=-0,58, p < 0,02), the % of body fat (r=-0,59, p < 0,02) and the body mass index (r=-0,54, p < 0,05). Baseline plasma insulin-like growth factor (IGF-I) was within the normal range for prepubertal children, with a mean ± SEM of 0,77 ± 0,09 U/ml.In conclusion, prepubertal girls with Turner Syndrome have a blunted GH response to GRF; in contrast to children with hypothalamo-pituitary insufficiency, they have normal plasma IGF-I. Our data suggest that the decreased GH response to GRF of Turner Syndrome patients may result from excess body fat.

58 EVALUATION OF GROWTH AND ENDOCRINE FUNCTIONS AFTER BONE MARROW TRANSPLANTATION (BMI) FOR MALIGNANCIES

Total body irradiation (TBI) is used in preparation for BMI and in order to evaluate the course of growth and endocrine disturbances an extensive follow-up has been designed. 17 children, aged 2.4-17.8 years received BMI for ALL (n=14), AML (n=2) and CML (n=l). Median height SDS in 14 children below age 15 was at time of BMI +0.48 (range -1.42 to 1.60) and after 12 months +0.12 (-1.16 to 1.20) (p<0.05). Those followed for 24 (n=9) and 36 months (n=6) had no significant fall in height SDS. Serum somatomedin C in the 6 cases followed for 36 months was normal. Peak growth hormone values after clonidine showed great variation and the results were inconclusive. Primary hypothyroidism was found in one case and elevated TSH values in 3 with T4 in normal range. No evidence of TSH insufficiency was seen. In all 8 girls above 10 years ovarian insufficiency developed and all were in need of replacement therapy. Of 2 boys above 10 years one had subnormal serum testosterone and one had bilateral orchiectomy performed. 6 of 7 boys below 10 years had normal gonadotropin response to LHRH and one was hyperresponsive. No evidence of gonadotropin insufficiency was found. Although preliminary, our data show that growth retardation does not seem to be of major importance whereas gonadal deficiency is pronounced and thyroid deficiency may be frequent. More data are needed and a detailed and prolonged endocrine follow-up seems essential.

Decreased growth hormone (GH) response to oral clonidine in endemic cretinism: effect of L-T3 therapy.

As GH secretion is dependent upon thyroid hormone availability, the GH responses to clonidine (150 micrograms/m2) and the TSH and PRL response to TRH were studied in eight endemic (EC) cretins (3 hypothyroid, 5 with a low thyroid reserve) before and after 4 days of 100 micrograms of L-T3. Five normal controls (N) were also treated in similar conditions. Both groups presented a marked increase in serum T3 after therapy (N = 515 +/- 89 ng/dl; EC = 647 +/- 149 ng/dl) followed by a decrease in basal and peak TSH response to TRH. However, in the EC patients an increase in serum T4 levels and in basal PRL and peak PRL response to TRH after L-T3 therapy was observed. One hypothyroid EC had a markedly elevated PRL peak response to TRH (330 ng/dl). There were no significant changes in basal or peak GH values to treatment with L-T3 in normal subjects. In the EC group the mean basal plasma GH (2.3 +/- 1.9 ng/ml) significantly rose to 8.8 +/- 3.2 ng/ml and the mean peak response to clonidine (12.7 +/- 7.7 ng/ml) increased to 36.9 +/- 3.1 ng/ml after L-T3. Plasma SM-C levels significantly increased in N from 1.79 +/- 0.50 U/ml to 2.42 +/- 0.40 U/ml after L-T3 (p less than 0.01) and this latter value was significantly higher (p less than 0.05) than mean Sm-C levels attained after L-T3 in the EC group (respectively: 1.14 +/- 0.59 and 1.78 +/- 0.68 U/ml). These data indicate that in EC the impaired GH response to a central nervous system mediated stimulus, the relatively low plasma Sm-C concentrations, and the presence of clinical or subclinical hypothyroidism may contribute to the severity of growth retardation present in this syndrome.

Growth hormone (GH) response to a single intravenous injection of synthetic GH-releasing hormone in prepubertal children with growth failure.

In this collaborative study involving 27 European medical centers, the plasma GH response to a single iv bolus dose of 2 micrograms/kg BW synthetic GHRH-(1-44)NH2 was determined in 574 children with growth failure of various etiologies. Analysis of the plasma GH response to GHRH was performed in 394 validated prepubertal children; these children were subdivided into 3 groups according to the degree of GH deficiency assessed within 6 months by conventional provocative tests (insulin, arginine, etc.): normal GH status (n = 210), partial GH deficiency (n = 73), or severe GH deficiency (n = 111). The mean peak GH values (+/- 2 SEM) after GHRH treatment in the three groups were 45.8 +/- 4.8, 29.2 +/- 6.3, and 16.8 +/- 3.1 microU/mL, respectively, and were greater than those after the conventional tests. The GH responses were consistent with the degree of GH deficiency based on the responses to the conventional tests. In addition, the areas under the GH response curves in the three groups were significantly different (P less than 0.0001). Among children with severe idiopathic GH deficiency 77% had a peak plasma GH level after GHRH above 10.0 microU/mL and 39% had a peak GH above 20.0 microU/mL. In these children, a single GHRH injection provides information on both their GH secretory capacity and the putative supresellar etiology of their GH deficiency, and may be of potential therapeutic value.

Effect of oral administration of L-dopa on the plasma levels of growth hormone-releasing hormone (GHRH) in normal subjects and patients with various endocrine and metabolic diseases

The responses of plasma growth hormone-releasing hormone (GHRH) and growth hormone (GH) to oral administration of L-dopa were studied in normal subjects and patients with various endocrine and metabolic diseases to clarify the pathophysiological role of the GHRH-GH axis. In normal subjects, the plasma GHRH concentration was increased from the basal value of 9.8 +/- 1.4 pg/ml (mean +/- SE) to 34.8 +/- 3.1 pg/ml at 30 approximately 90 min after oral administration of 500 mg L-dopa, followed by a rise of GH release (plasma GH level from less than 1 ng/ml to 21.7 +/- 4.7 ng/ml) in most cases, indicating that L-dopa stimulates GH secretion via hypothalamic GHRH. On L-dopa administration, no apparent increases in both plasma GHRH and GH concentrations were observed in patients with hypothalamic hypopituitarism, whereas GHRH administration induced almost normal GH response. In patients with acromegaly, the plasma levels of GHRH remained stationary after the L-dopa administration and did not correlate with plasma GH levels. In subjects with simple obesity, the responses of plasma GHRH (peak 13.2 +/- 1.2 pg/ml) and GH (peak 4.3 +/- 1.7 ng/ml) to L-dopa were significantly lower than those in normal subjects (p less than 0.01). In patients with primary hypothyroidism, peak levels of plasma GHRH (12.6 +/- 1.3 pg/ml) and GH (2.4 +/- 0.6 ng/ml) were significantly lower than those in normal subjects (p less than 0.01). In patients with non-insulin dependent diabetes mellitus (NIDDM), the responses of GHRH and GH were divided into 2 groups; in the responder the peak values of GHRH and GH were 19.4 +/- 8.6 pg/ml and 12.2 +/- 1.4 ng/ml and in the low or non responder 14.7 +/- 1.5 pg/ml and 2.0 +/- 0.6 ng/ml, respectively. Between both groups, there was a significant difference in the values of fasting blood sugar and HbA1 and mean suffering period. These findings suggest that GH secretion evoked by the L-dopa administration is induced by GHRH released from the hypothalamus, and impairment of GH secretion associated with simple obesity, primary hypothyroidism, or NIDDM may be in part attributed to insufficiency of GHRH release from the hypothalamus, and indicate that L-dopa test is clinically useful for evaluating the ability of intrinsic GHRH release in such diseased states.

Bromocriptine does not alter growth hormone (GH) responsiveness to GH-releasing hormone in acromegaly.

GHRH (100 micrograms) and TRH (200 micrograms) were administered to 24 active acromegalic patients before and during chronic bromocriptine (Br) treatment (Br, 10-15 mg/day for 3-5 months) to evaluate the possible effects of the dopamine agonist on GH release induced by these releasing hormones. Mean daily plasma GH levels were reduced by Br treatment from 34 +/- 40 (SD) to 16 +/- 19 ng/ml (P less than 0.01). No significant changes were found when comparing the GH response to GHRH as mean area under the response curve (nanograms per min/ml above the basal) (pretreatment, 5453 +/- 7843; during Br, 7017 +/- 12763 ng/ml . min), and as mean individual peak GH values (pretreatment, 130 +/- 148; during Br, 126 +/- 187 ng/ml) before and during treatment. The percentage GH increase (pretreatment, 340 +/- 354; during Br, 617 +/- 539%) was however significantly higher during Br. Br treatment significantly reduced the GH response to TRH in terms of mean of individual peak levels (from 136 +/- 134 to 60 +/- 52 ng/ml; P less than 0.01) and area under the response curve (from 3142 +/- 3998 to 1331 +/- 1646 ng/min . ml; P less than 0.01). However, the percentage GH increase was not significantly different (pretreatment, 486 +/- 729; during Br, 1059 +/- 1862%). When the patients were divided into Br responders, i.e. mean daily GH reduction during Br of at least 50% below baseline, and nonresponders, the initial response to GHRH was significantly higher in the latter group, but was unaffected by Br treatment in either group. On the contrary, the response to TRH, statistically significant initially only in the Br responder group, was reduced by Br treatment. We suggest that cells sensitive to Br and TRH but not to GHRH (lactotroph-like) and cells sensitive to GHRH but not to Br (pure somatotrophs) may coexist in GH-secreting adenomas.

The relationships of neukoendocrine tests in endogenous depression

1. 1. Amphetamine induced growth hormone (GH) response (Study 1) and TRH Induced TSH response (Study 2) were assessed in patients with endogenous depression (n = 20 and n = 22, respectively), who underwent a dexamethasone suppression test (DST) on the following day. 2. 2. The GH response to the amphetamine was significantly lower in the group of depressed patients than in the healthy controls (n = 13). 3. 3. There was no difference between the DST nonsuppressors (n = 12) and suppressors (n = 8) in the GH peak values. This data strongly suggests that the two tests are independent from each other. 4. 4. There was no significant relationship between the DST and TRH-TSH results. 5. 5. Patients with blunted TSH response to TRH have had significantly higher cerebrospinal fluid 5-HIAA levels.

Failure of β-endorphin antiserum, naloxone, and naltrexone to alter physiologic growth hormone and insulin secretion

The role of endogenous opiate-like peptides in physiologic regulation of growth hormone (GH) and insulin (IRI) secretion was assessed by passive immunization with β-endorphin antiserum and by administration of the opiate antagonists naloxone and naltrexone. Six-hour secretory profiles were obtained from 5 groups of freely-moving chronically cannulated male rats following the i.v. administration of (I) β-endorphin antiserum, (II) normal rabbit serum, (III) naloxone (1 mg/kg), (IV) naltrexone (1 mg/kg), and (V) normal saline. The typical ultradian rhythm of GH secretion was evident in all groups with most peak GH values >400 ng/ml. No disruption in amplitude of periodicity of the GH rhythm was observed and there was no significant difference in mean 6-hr plasma GH levels. Plasma IRI levels fluctuated minimally over the 6-hr sampling period. There was no significant difference in mean 6-hr IRI levels between groups I and II, or between groups III, IV and V. These data do not support the view that endogenous opiate-like peptides play a physiologically important role in maintaining basal GH and IRI secretion.

COMBINED TEST OF HYPOTHALAMIC‐PITUITARY FUNCTION IN GROWTH RETARDED CHILDREN TREATED WITH GROWTH HORMONE I. Secretion of Growth Hormone and Somatomedin before and after Treatment

In 23 growth retarded children two consecutive insulin tolerance tests (ITT) were performed to establish a diagnosis of growth hormone (GH) deficiency. Nine children did not respond (GH peak value less than 8 mU/1), whereas 14 were classified as having partial GH deficiency (GH peak value less than 20 mU/1). All were treated for an average period of 40 months with human growth hormone (HGH). In a combined stimulation test at the end of the treatment period 9 children demonstrated a persistent GH deficiency, whereas a normal response was found in 14 of the previous partial GH deficient children. During treatment the monthly growth rate rose from 0.21 cm 0.58 cm in the GH deficient children and from 0.31 cm to 0.70 cm in the partial deficient children, in most of whom spontaneous pubertal development occurred during treatment. Somatomedin (SM) values were decreased in the GH deficient children before and after treatment but increased to normal levels during treatment. Growth velocity in these children during treatment was correlated to SM values before treatment. In the partial GH deficient children SM values were subnormal before but normal after treatment. This supports the assumption that in some children with constitutional delay in puberty a reversible functional hypopituitarism exists, which is normalized after the onset of puberty, due to androgens sensitizing growth hormone releasing mechanisms. Treatment with HGH may induce increased growth velocity in some of these patients.

Effect of hyperglycemia on the growth hormone response to L-dopa in diabetic subjects.

Plasma growth hormone (GH) levels were measured before and after oral administration of L-dopa in 8 insulin-dependent juvenile diabetic patients, and in 6 non insulin-dependent maturity-onset diabetics, while they were hyperglycemic, and values were compared with those of normal children and adult subjects. Maturity-onset diabetics failed to show an increase in serum GH levels after L-dopa administration, while serum peak GH values of juvenile diabetic patients were not significantly different from those of normal adults and children. Hyperglycemia thus failed to prevent L-dopa induced growth hormone response in insulin-dependent juvenile diabetic patients.

Effects of selective sleep deprivation on sleep-linked prolactin and growth hormone secretion.

1. The secretion of prolactin and growth-hormone (hGH) was investigated during sleep in 10 healthy volunteers (8 males and 2 females): The comparison of one baseline night, one night after daytime physical exercise, and one night with selective deprivation of sleep stages 3 and 4 and paradoxical sleep showed clear differences of prolactin and hGH secretion during sleep. 2. Prolactin secretion is entrained into the sleep cycle of Non-REM and REM periods. A maximum of plasma hormone elevations occurs during the first quarter of sleep cycles, i.e., during Non-REM periods and less frequent rises at the end of the cycles, mainly during REM periods. 3. In contrast to growth hormone, concentrations of prolactin remain high also during later cycles occurring toward morning. This shows that high prolactin, but not high concentrations of hGH, regularly occur during sleep cycles with small amounts of slow-wave sleep. 4. Maximal prolactin concentrations during sleep are affected neither by preceding daytime physical exercise nor by selective deprivation of slow sleep stages 3 and 4. This is further evidence that slow-wave sleep stages are not necessary for the development of high plasma prolactin concentrations. However, peak values of growth hormone in the first and second cycle are significantly diminished after selective deprivation of sleep stages 3 and 4. 5. In abnormally long sleep cycles with artificial delay of the first REM period, the cyclical rhythmicity of prolactin release seems disturbed. This is further evidence for the sleep-dependent rhythmicity in the secretion of this hormone.

Growth hormone release following thyrotrophin-releasing hormone injection into patients with anorexia nervosa.

The effect of thyrotrophin-releasing hormone (TRH) or luteinizing hormone-releasing hormone (LH-RH) on plasma levels of growth hormone (GH), prolactin (PRL), thyrotrophin (TSH), and luteinizing hormone (LHY, were studied in patients with anorexia nervosa. The basal plasma GH levels were elevated in 6 of 11 patients studied. Intravenous injection of synthetic TRH T500 mug) significantly raised the plasma GH levels in 9 of 11 patients. The peak values of plasma GH after TRH ranged from 6.0 to 31.5 ng/ml. Plasma GH concentrations also increased following the administration of synthetic LH-RH (100 mug) 1 of 7 patients. The intravenous injection of saline solution caused no significant change in plasma GH in these patients. The plasma LH responses to LH-RH were significantly blunted in all patients, whereas the plasma PRL and TSH responses to TRH were almost normal in the patients examined. These results suggest that the hypothalamo-pituitary function regulating GH and LH secretion is altered in patients with anorexia nervosa.