Complete Growth Hormone Deficiency Research Articles

Familial congenital hypopituitarism with central diabetes insipidus.

Congenital hypopituitarism (CH) presenting with central diabetes insipidus is typically associated with midline facial deformities or ophthalmological abnormalities. We present three brothers with CH and central diabetes insipidus not associated with any of these predisposing conditions. All three subjects presented with clinical features typical for CH (neonatal hypoglycemia, short stature, protruding forehead, and microgenitalia). All had hypoplastic genitalia indicating in utero gonadotropin deficiency, and all had complete GH deficiency. One represented low levels of thyroid hormones and TSH, indicating central hypothyroidism. Water deprivation examination in two of the brothers demonstrated complete arginine vasopressin deficiency in one and partial deficiency in the other. Magnetic resonance imaging indicated absence of the pituitary stalk, severe hypoplastic anterior pituitary in all three brothers, and absence of any posterior pituitary gland in two of the three. The other sibling had an ectopic posterior pituitary. This first report of familial CH with central diabetes insipidus may represent a previously unknown midline anomaly and provide new insights into the genetic control of pituitary and hypothalamic development.

PRETREATMENT 15N-RETENTION TEST (15N-T), BUT NOT IGF 1-GENERATION TEST (IGF 1-GT) DIFFERENTIATES BETWEEN COMPLETE AND PARTIAL GROWTH HORMONE DEFICIENCY

15N-T and IGF 1-GT were studied by correlating shortterm effects to subsequent growth velocity (GV) during therapy. Methods: Nitrogen excretion Using the stable isotope 15N and IGF 1 were measured before and after 2 IU rHGH/m2 BW s.c. on 3 consecutive days in patients with complete growth hormone deficiency (cGHD, n=17). partial GHD (pGHD, n=16) and normal variant short stature (NVSS, n = 18). Only cGHD and pGHD patients were treated for 1 year with rHGH (12 IU/m2xwk). Before treatment there were no significant differences in auxological data between the 3 groups; 15N-T, IGF 1-GT and growth velocity (GV) were compared with GV in the subsequent year either with rHGH-therapy (cGHD and pGHD) or without (NVSS). 15N-excretion was measured by isotope masspectrometry. IGF 1 was determined by a RIA after extraction. Results: The effect of rHGH-administration on the 15N-T differed significantly between the 3 groups. The best response (143±6.9% 15N-retentlon) was seen in the cGHD group, while 130.1±16,4% (P<0.001) in the pGHD and 108.9±6,4% (p<0,001)ln the NVSS group were reached. The IGF 1-GT did not show any differences between the three groups of patients. After 1 year of rHGH therapy GV was 11,3±3 cm/a in the cGHD and 7.6±2,2 cm/a in the pHGH group. The GV in the untreated NVSS patients was significantly lower (4,2±1,7 cm/a) compared to the cGHD (p<0,001) and the pGHD (p<0.001) patients. The 15N-T can discriminate between patients with complete and partial GHD and patients with short stature after only 3 injections of rHGH. A correlation between 15N-T and GV after 1 year of rHGH treatment was seen in the pGHD group (r=0,87). IGF 1-GT as well GV before treatment were not suitable to predict growth hormone response in any group. Conclusions: In this study the 15N-T was reliable in differentiating the 3 groups of patients and in predicting the response to growth hormone treatment in patients with pGHD.

Clinical Application of Urinary Growth Hormone (GH) to the Screening of GH Deficiency

We measured GH in the morning urine (U-GH) of 270 normal subjects aged three to 20 years. U-GH in patients with GH deficiency were compared with those of the normal controls. In normal subjects, U-GH showed a significant change with age. They were high in midpuberty, reaching a peak at 11 to 12 years in girls and at 13 to 14 years in boys. U-GH in patients with complete GH deficiency were apparently lower than those of the normal, while the U-GH in patients with partial GH deficiency overlapped with the normal range. A positive correlation was found between U-GH in GH- deficient patients and their height velocity before GH treatment. A negative correlation was found between U-GH and increment of height velocity after treatment. Screening of complete GH deficiency can be done by measuring U-GH. U-GH was also suggested to be useful as an index for the necessity of GH treatment.

Growth of infants with neonatal growth hormone deficiency.

In view of contradictory reports on the growth hormone dependency of early postnatal growth we studied the growth curves of 15 infants with neonatal growth hormone deficiency. In seven infants the growth curve was parallel to the standards of the infancy-childhood-puberty (ICP) model (group 1), but in the remaining infants there was an immediate deviation of the growth curve (group 2). In this group the mean (SD) at 4 and 9 months of age was -3.3 (1.1) and -4.9 (1.4), respectively, when compared with the ICP model. The mean birth length in both groups was decreased and five out of 15 had a birth length of less than -2 SD. Serial measurements of the growth hormone response to provocation tests in two patients in group 2 showed decreasing concentrations, while four patients with documented complete growth hormone deficiency belonged to group 2. We conclude that growth hormone is needed for early infant growth and that the normal growth pattern in some infants with neonatal pituitary dysfunction is due to incomplete insufficiency.

Low urinary growth hormone values in patients with Turner's syndrome.

Short stature is one of the major symptoms in Turner's syndrome (TS). The cause of short stature is not clearly known at present. In this study we initially assessed GH secretory status in TS by determinations of urinary human (h) GH excretion for 2 consecutive days. Secondly, the therapeutic dose of hGH used for treatment of short stature in TS was evaluated by measurements of urinary hGH after recombinant hGH (r-hGH) injections. Twenty-four-hour urinary hGH excretion for the 2 days combined was significantly lower in patients with TS than in normal children [2.3 +/- 1.8 ng/day (n = 7) vs. 13.4 +/- 3.2 (n = 16); P less than 0.001], although four of seven patients with TS had normal GH responses to the provocative tests. The mean level of urinary hGH in TS after 2 days was comparable to that in complete GH deficiency (1.9 +/- 0.9 ng/day; n = 14) that we previously reported. Treatment with daily sc injections of 1.0 IU (0.37 mg)/kg.week r-hGH, given in seven divided doses, normalized urinary hGH excretion and induced remarkable catch-up growth in all patients with TS. These results indicate that the 24-h endogenous GH secretion in seven patients with TS is impaired. The measurement of 24-h urinary hGH excretion may prove to be useful as a marker to assess the abnormal GH secretion and the adequacy of treatment with hGH in patients with TS. The therapeutic dose of hGH in TS is approximately 0.37 mg/kg.week, given in seven divided doses. To convert international units of r-hGH to milligrams, divide by 2.7.

Chemical pathology of growth disorders

Growth disorders are characterized by two parameters - the absolute height measurement and the height velocity. The causes of growth failure can be classified as follows : endocrine, psychological, iatrogenic, chromosomal, nutritional, intrauterine, chronic disease and skeletal. I shall concentrate on the endocrine causes of disordered growth, in particular, abnormalities in the production of growth hormone (GH). Other endocrine abnormalities causing short stature include deficiency of thyroxine, excess Cortisol and delay in the production of sex steroids at puberty. GH is released from the anterior pituitary in a pulsatile fashion, with the greatest secretion occurring about one hour after the onset of sleep. Secretion of GH is stimulated by growth hormone releasing hormone (GHRH) and inhibited by somatostatin, both these peptides being released from the hypothalamus. GH exerts its growth promoting effects principally by acting on tissues, such as cartilage and muscle, to produce insulin-like growth factor I (IGFI) which probably acts locally in a paracrine fashion to stimulate growth. The clinical features of severe GH deficiency are relatively easy to recognize, but are less apparent in the child with partial lack of GH. The approach to the diagnosis of abnormal secretion of GH must include a complete clinical assessment, with appropriate auxological data and bone age. Provocation tests, to establish either partial or complete deficiency of GH, are based on either pharmacological or physiological stimuli. Other tests, used mainly for research, include measurement of the GH pulses over 24 hours, GHRH stimulation test and urinary GH excretion. 1GF1 measurement is of limited value in GH deficiency, but useful in states of GH excess. The introduction of biosynthetic GH has resulted in a broader spectrum of patients with growth disorders receiving treatment, and there is no longer the risk of transmission of slow virus infection, as occurred with the use of GH extracted from human pituitaries.

Stimulation of nitrogen and whole-body protein metabolism in growth hormone-deficient children by recombinant human growth hormone: relationship to growth.

The effect of a mammalian-cell-derived recombinant human growth hormone (rhGH) on nitrogen and whole-body protein metabolism was assessed in 12 children with complete growth hormone (GH) deficiency. All the patients received single oral doses of 15N-glycine (95 atom % 15N), 20 mg/kg body weight, prior to and following 7 days of treatment with rhGH, 1.7 IU/m2 body surface area (BSA) per day, administered subcutaneously. Prior to rhGH, mean urinary 15N-nitrogen excretion was 42.8 +/- 8% of the administered dose, which fell significantly to 22.8 +/- 7% during rhGH administration (p < 0.0001). Stimulation of protein metabolism by rhGH resulted in a protein net gain rate of 1.1 +/- 0.4 g/kg/day, which was significantly higher than the 0.6 +/- 0.5 g/kg/day rate seen prior to rhGH (p < 0.001). In patients subsequently placed on daily subcutaneous injections of rhGH 1.7 IU/m2 BSA, mean height velocity standard deviation score (HV SDS) for chronological age significantly increased from -3.8 +/- 2.6 to +8.5 +/- 3.1 and +3.3 +/- 2.2, during the 1st and 2nd years of treatment, respectively. However, there was no correlation between the long-term response to rhGH treatment and the short-term changes in nitrogen or protein metabolism in GH-deficient children.

Measurement IGF-I in human blood by immunoenzymometric assay

Insulin-like growth factor-I (IGF-I) is the growth factor which binds to its specific binding proteins in plasma and mediates most of the actions of growth hormone (GH). In terms of this, measurement of IGF-I concentrations is considered to be important in the diagnosis and treatment of growth abnormalities. In the present report we describe a modified immunoenzymometric assay (IEMA) for IGF-I using monoclonal antibody and peroxidase conjugated polyclonal antibody, which was originally developed by Tamura et al. The minimum detection level was 3ng/ml and good linearity was obtained at a range of 3-50ng/ml. The recovery of added IGF-I was nearly quantitative, and cross reaction with human IGF-II was less than 1%. There was a significant positive correlation between the IGF-I values determined by IEMA and by RIA. We measured the levels of IGF-I by this IEMA in normal subjects and children with short stature. Serum or plasma samples were extracted by acid-ethanol method. In normal children IGF-I level was observed age-dependently. IGF-I values gradually increased and reached peak levels (101.2-473.2ng/ml) in pubertal period and thereafter decreased to adult levels (67.3-329.6ng/ml). In subjects with short stature older than 5 yrs, the percentages falling below the normal mean for chronological age by at least 2SD were 100% for complete GH deficiency (n = 5), 80.0% for partial GH deficiency (n = 15), 25.0% for GH neurosecretory dysfunction (n = 4), 40.0% for non-endocrine short stature (n = 60) and 25.0% for Turner syndrome (n = 4). In children younger than 4 yrs, it may be difficult to use IGF-I for diagnosis of GH deficiency because there was an overlap in IGF-I values with normal children. IEMA for IGF-I is shown to be a reliable method for measurement of IGF-I in blood and is appropriate for diagnosis of growth disorders with short stature in subjects older than 5 yrs.

Epidemiologic survey of patients treated with growth hormone in France in the period 1959-1990: preliminary results.

Because the delivery of growth hormone (GH) was centralized from 1977 in France, it has been possible to conduct, during the second half of 1990, a nationwide survey of the health status of patients treated with GH from the year 1959. A questionnaire regarding the 5,546 patients recorded for the period 1959-1990 was sent to the prescribers or the patients. 5,418 more or less completely documented reports were obtained. The mean age of the patients at the onset of GH treatment was 11.0 +/- 4.1 years. 1,937 of them had at this time some important disease associated with GH deficiency. The mean duration of treatment was 3.99 +/- 3.05 years. 3,446 patients were still under follow-up. Very recent information (1990-1991) was given for 82.7% of patients, less recent data (1985-1989) for 13.4%. For 3.9%, no data beyond 1985 were obtained. 77 patients had died, 38 from neoplastic disease (mainly recurrence of a primary malignancy), 10 from accident, 3 by suicide, 7 with neurological disease [only 1 case of Creutzfeldt-Jakob disease (CJD) was reported at the time of the survey], the others from various causes. No abnormal frequency of posttreatment leukemia, lymphoma, malignancies, hip diseases, glucose intolerance or other disease focusing attention, was found in the survey. From the time when this survey was completed (December 1990) to that of this report (May 1992), other cases of CJD have been reported in France: 3 ascertained, 7 clinically resembling but not yet certain. These 10 patients were treated for complete GH deficiency, 6 of congenital or neonatal cause and 4 after neurosurgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness and limitation of measurement of insulin-like growth factor binding protein-3 (IGFBP-3) for diagnosis of growth hormone deficiency.

To analyze the utility of insulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay for diagnosis of growth hormone deficiency (GHD) we measured IGFBP-3 in sera from normal children, short children and patients with GHD. The sensitivity (true positive ratio) of IGFBP-3 for complete GHD (cGHD) was 93%, while the specificity (true negative ratio) for normal short children (NS) was 88%. In contrast, the sensitivity of IGFBP-3 for partial GHD (pGHD) was only 43%. The poor discrimination between patients with pGHD and NS may be the result of their relatively similar GH level, as compared to cGHD, or due to the limitations of GH stimulation tests. The specificity of IGFBP-3 for NS was excellent in children of all ages: less than 10 years old (87%) and older than 10 (88%). However, sensitivity for GHD was good for children less than 10 years old (84%) but poor for children older than 10 (64%). IGFBP-3 may be less sensitive for diagnosing GHD in older children because IGFBP-3 levels may also increase during puberty due to mechanisms independent of the GH-IGF-I axis.

Hallermann‐Streiff syndrome with hypopituitarism contributing to growth failure

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.

Growth Hormone Secretion and the Therapeutic Effects of Human Growth Hormone: First Japanese Results of the Kabi Pharmacia International Growth Study/International Cooperative Growth Study

Data for a total of 942 new cases of hypopituitarism, out of 3493 patients treated with recombinant human growth hormone (GH) for more than 1 year, have been analysed. The mean peak GH correlated well with clinical variables related to growth and was considered to be a good index of GH secretory capacity. Mean peak GH was correlated inversely with obesity (r = -0.253, p less than 0.01). The lower the height velocity before treatment, the mean peak GH and the height SDS, the greater was the therapeutic effect achieved. The patients with mean peak GH less than or equal to 5 ng/ml were defined as having complete GH deficiency (GHD), and those with a mean peak GH of 5-10 ng/ml as having partial GHD. The clinical entity of GH neurosecretory dysfunction could not be identified from either the clinical variables examined or the therapeutic effect. The appearance of GH antibody was considered to be of no clinical significance because its incidence and titre were both low.

Biosynthetic growth hormone therapy in children with growth hormone deficiency: Experience at AIIMS, New Delhi

A total of 20 previously untreated children with growth hormone deficiency (GHD) were treated for one year with biosynthetic human growth hormone (hGH). The mean chronologic age was 9.43 +/- 3.52 years with a height age of 5.02 years, and bone age 9.43 +/- 3.52 (TW2-RUS) 6.42 years. The mean pretreatment growth velocity was 2.43 +/- 0.90 cm/year. Of these 14 children had complete GHD (peak GH levels less than 5 ng/ml) and 6 had partial GHD. They were treated with recombinant GH in a dose of 0.5 IU/kg/week divided into 6-7 injections per week subcutaneously at night. The mean growth velocity increased to 8.88 +/- 2.10 cm/yr at the end of 6 months and 8.00 +/- 2.21 cm/yr at 12 months. The actual gain ranged from 6-11 cm in a year. There were no local adverse reactions. One child developed vitiligo of the face and another transient hyperglycemia.

Urinary Human Growth Hormone Measurement Using a Highly Sensitive Sandwich Enzyme Immunoassay: Diagnostic and Therapeutic Uses in Patients with Growth Hormone Deficiency*

Several reports indicate that urinary hGH excretion is significantly lower in patients with either partial (PGHD) or complete GH deficiency (CGHD) than in normal but short children (NSC) or normal children (NC). However, there is an overlap between the NSC and NC groups and the PGHD group. Using a highly sensitive sandwich enzyme immunoassay, we investigated whether the measurement of urinary hGH can clearly separate the PGHD and CGHD groups from the NSC and NC groups. In addition, we measured the urinary excretion of synthetic methionyl-hGH (met-hGH) in PGHD and CGHD after sc injections of 2 and 4 IU and im injections of 4 IU in an attempt to determine the optimal replacement dose. Total 24-h urinary hGH excretion in each patient examined for 2 consecutive days varied from 1 day to the next. There were no differences in urinary hGH excretions between the NSC group and the NC group. The lower values for daily urinary hGH excretion in the NSC group overlapped some of the higher values in the PGHD group. However, when the mean urinary hGH level of both days was used, the 24-h urinary hGH excretion clearly separated the PGHD (5.5 +/- 2.3 ng/day; range, 1.3-9.2; n = 21) and CGHD (1.9 +/- 0.9 ng/day; range, 0.6-3.6; n = 14) groups from the NSC (12.8 +/- 3.1 ng/day; range, 9.3-17.5; n = 10) and NC (14.6 +/- 3.1 ng/day; range, 10.6-19.0; n = 6) groups without any overlap. A mean urinary hGH value less than 9.0 ng/day during a 2-day collection strongly suggested GH deficiency. Ten of 16 patients with PGHD and CGHD who received 2 IU met-hGH, sc, had urinary hGH levels within the range of the mean +/- SD in NSC. These patients received daily sc 0.097 +/- 0.024 IU/kg hGH injections. These results suggest that the measurement of 24-h urinary hGH excretion is noninvasive, accurate, and useful for the screening of GH deficiency. The mean value on 2 days of 24-h urinary hGH excretion for the screening of GH deficiency is estimated to be less than 9.0 ng/day. The optimal dose of GH as therapy for GH deficiency is demonstrated as daily sc injection of 0.1 IU/kg hGH, 0.7 IU/kg/week. To convert international units of met-hGH to milligrams, divide by 2.4.

Neurohypophyseal function of an ectopic posterior lobe in patients with growth hormone deficiency

We studied the neurohypophyseal function of 20 patients with complete GH deficiency owing to pituitary stalk transection by means of the water deprivation and the hypertonic saline infusion test. In T1-weighted magnetic resonance images, high-signal intensity of the posterior lobe of the hypophysis was missing in all the patients. An ectopic posterior lobe was observed at the proximal stump of the transected stalk in 17 patients, whereas the 3 patients without ectopic posterior lobe had overt diabetes insipidus or intractable nocturnal enuresis. After water deprivation, 3 patients with large ectopic posterior lobes (length along the pituitary stalk axis exceeding 5 mm) showed urinary osmolality and plasma AVP levels as high as those of 13 patients with partial GH deficiency in whom magnetic resonance images revealed no abnormalities. On the other hand, 14 patients with small ectopic posterior lobes (length less than 5 mm) showed significantly lower urinary osmolality and plasma AVP levels than the patients with large ectopic posterior lobes (p less than 0.01 and p less than 0.01, respectively) and the patients with partial GH deficiency (p less than 0.01 and p less than 0.01, respectively). Urinary osmolality in the patients with small ectopic posterior lobes, however, was higher than that in 3 patients without ectopic posterior lobes (p less than 0.01). During the hypertonic saline infusion test, peak plasma AVP levels in the patients with small ectopic posterior lobes were significantly lower than those in the patients with partial GH deficiency (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Usefulness of Urinary Growth Hormone Measurement in Short Children

Growth hormone (GH) levels in nocturnal urine were measured in 96 short children and 73 children of normal height in order to investigate whether urinary GH levels reflect spontaneous GH secretion and whether they might be used to screen short children for GH treatment. GH levels in 24-hour urine samples were significantly correlated with urinary albumin and beta 2-microglobulin levels in normal children, demonstrating an influence of renal function on urinary GH measurements. Nocturnal urinary GH levels showed significant positive correlations with mean serum GH levels during 3 hours of sleep (r = 0.26, p less than 0.05) and plasma insulin-like growth factor I (IGF-I) levels, reflecting physiological GH secretion. Urinary GH levels were significantly lower in the eight children with complete GH deficiency (3.1 +/- 2.3 ng/g creatinine) than in the normal children (13.8 +/- 11.2 ng/g creatinine). Urinary GH levels in three other groups of short children, partial GH deficiency (11.1 +/- 16.9 ng/g creatinine), impaired GH secretion during sleep (10.4 +/- 12.6 ng/g creatinine) and non-endocrine short stature (18.8 +/- 19.5 ng/g creatinine), were not significantly different from those in the normal children. However, when the cut-off point for defining GH insufficiency was set at 5 ng/g creatinine, 87.5% (21 out of 24) of the short children with low urinary GH levels were suitable subjects for GH treatment (i.e. had complete GH deficiency, partial GH deficiency or impaired GH secretion during sleep).(ABSTRACT TRUNCATED AT 250 WORDS)

Age‐Related Changes in Urinary Growth Hormone Level and Its Clinical Application

In order to establish the normal range of urinary growth hormone (GH) level for age and sex, which is important in the clinical application of urinary GH to diagnosis, we measured GH in the first morning urine specimens of 270 normal subjects aged 3 to 20 years. Urinary GH levels in patients with documented GH deficiency were compared with those of the normal controls. In normal subjects, urinary GH levels showed a statistically significant change with age. They were relatively high in infancy and mid-puberty, reaching a peak at 11 to 12 years in girls and at 13 to 14 years in boys. Urinary GH levels in patients with complete GH deficiency were apparently lower (less than -2.0 SD) than those of the normal children, while the levels in patients with partial GH deficiency overlapped with the normal range. When assessing GH secretion by using urinary GH measurement, consideration of age and sex is required, since the level changes significantly with these factors.

Growth Hormone Secretion during Sleep

The serum levels of insulin-like growth factor I (IGF I), dehydroepiandrosterone sulfate (DHAS), testosterone (T) and estradiol (E2) have been measured in 78 prepubertal and 57 early pubertal patients referred for short stature, at the same time when their secretion of GH was evaluated both during nocturnal sleep and by two conventional stimulation tests. According to the results of GH measurements they were considered as having a normal secretion of GH (group I), a complete GH deficiency (group II), a partial GH deficiency (group III), low responses to stimuli with normal secretion during sleep (group IV) or a nocturnal neurosecretory dysfunction (group V). Though widely scattered, the IGF I levels showed the following characteristics: a significant increase at puberty from 0.77 to 1.29 U/ml (p less than 0.001) in the so-called endocrinologically normal patients of group I, not in the other groups; in the prepubertal patients of group I, a correlation of IGF I with chronological age (r = 0.47, p less than 0.005) and bone age (r = 0.52, p less than 0.002); significantly reduced IGF I levels in patients of group II having complete GH deficiency (p less than 0.001); no significant differences between prepubertal patients with partial or atypical GH deficiency from groups III, IV, V and prepubertal patients from group I; lower pubertal levels in groups III, IV, V than in pubertal patients from group I (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic Limitations of Spontaneous Growth Hormone Measurements in Normally Growing Prepubertal Children

To evaluate whether the measurement of the spontaneous overnight growth hormone secretion in prepubertal children clearly separated normal children from subjects with growth hormone deficiency, we studied 45 prepubertal normally growing children (10 with normal height and 35 with constitutional growth delay) and compared their overnight growth hormone secretion with that of a group of subjects with either isolated growth hormone deficiency or neurosecretory dysfunction. Peak growth hormone levels (greater than or equal to 10 ng/mL) following oral clonidine administration were normal in individuals with normal height, constitutional growth delay, and neurosecretory dysfunction, as was the basal somatomedin C concentration; subjects with growth hormone deficiency had low peak growth hormone levels (less than 10 ng/mL) following oral clonidine administration as well as low basal somatomedin C values. The mean 9-hour overnight growth hormone concentration, total growth hormone output, total number of nocturnal pulses, and the mean peak growth hormone response during nocturnal sampling were similar in the normal height and constitutional growth delay groups and significantly greater than those seen in subjects with either growth hormone deficiency or neurosecretory dysfunction. Twelve (26.6%) of 45 normally growing children (4 to 10 normal height and 8 of 35 constitutional growth delay), however, had low overnight growth hormone levels (less than 3 ng/mL), which overlapped results obtained in the growth hormone-deficient or neurosecretory dysfunction groups. Frequent overnight growth hormone (GH) sampling does not always separate normal-growing children from those with partial or complete GH deficiency. In our this study over one quarter of the normally growing children had overnight GH levels in the range of children with either GH deficiency or neurosecretory dysfunction. These findings, in addition to the cost and difficulty in performing this test, do not support the measurement of spontaneous GH as a routine test in short but normally growing prepubertal children.

A highly sensitive sandwich enzyme immunoassay of urinary growth hormone in children with short stature, Turner's syndrome, and simple obesity

GH values were determined by a highly sensitive sandwich enzyme immunoassay in the 1st morning and/or 24-h accumulated urine samples in 94 children (short stature 70, including 14 with complete GH deficiency, 9 with partial GH deficiency, and 47 with GH-normal short stature; Turner's syndrome, 10, and simple obesity, 14). GH values were also determined in the 2nd to 4th urine samples taken on the same day together with the 1st morning urine in 5 of them. GH values in the 1st morning urine correlated significantly with those of the 24-h urine and with serum peak and mean GH values during nocturnal sleep as a physiological GH secretion test. The 2nd to 4th urines had lower GH concentrations than the 1st morning urine. The GH value of the 1st morning urine in complete GH deficiency was significantly lower than those in GH-normal short stature, partial GH deficiency and Turner's syndrome. However, no significant difference was detected in urinary GH values between complete GH deficiency and simple obesity. We conclude that 1st morning urinary GH estimation may be useful for differentiation of complete GH deficiency from other causes of short stature, but may be difficult for the distinction between complete GH-deficiency and obesity with normal GH secretory ability.