Urinary Growth Hormone Excretion Research Articles

Maturational changes of urinary growth hormone excretion in the premature infant.

High plasma GH concentrations are observed in the newborn infant. To characterize the maturational change of GH secretion in premature infants, we serially measured 24-h urinary GH excretion in 30 premature infants. The gestational age ranged from 25-37 weeks and birth weight from 468-2415 g. Urinary GH excretion at 1 week of age was negatively correlated with gestational age, birth weight, and length of infants with adequate intrauterine growth. In the infants with 27 weeks of mean gestation (range, 25-28 weeks) mean urinary GH excretion was highest (6.1 micrograms/day) at the first week, decreased to 1.2 micrograms/day by the fourth week, and remained between 0.05 and 0.18 micrograms/day thereafter. When compared to the corresponding conceptional age, there was no postnatal difference in the pattern of GH excretion between infants with 27 and 31 (range, 29-32) weeks of mean gestational age. Persistent hyperexcretion of GH was observed in 4 of the 5 infants with intrauterine or postnatal growth retardation. Our results suggest that the postnatal change of 24-h urinary GH excretion is similar to ontogenic changes of plasma GH in fetus, and GH may have some effects on postnatal growth in premature infants.

Urinary Growth Hormone Excretion as Measured by a Sensitive Immunochemiluminometric Assay

A sensitive immunochemiluminometric assay with a detection limit of 1.1 microU/L was developed for the measurement of urinary growth hormone (UGH). The assay was shown to be specific and precise. There was a good correlation between serum growth hormone (GH) and UGH concentrations in 20 patients with acromegaly and six volunteers following an intravenous injection of recombinant GH. We concluded therefore that UGH measurements appear to provide a satisfactory index of GH secretion. The use of the assay in the investigation of growth disorders was assessed. We studied 11 pre-pubertal children, six of normal stature, and five of short stature, over a 6-month period. Sequential fortnightly measurements of UGH were carried out and height velocity was determined. The children of short stature grew at a slower rate and excreted less GH than the children of normal stature. However, we observed considerable within-individual variability in GH excretion in both groups (CV 22-98%). We therefore recommend that sequential UGH analyses should be carried out and the results interpreted in conjunction with growth measurements. However, further investigations into the renal handling of GH are needed to establish optimum sampling regimes.

Is there a place for urinary growth hormone measurement?

The evaluation of growth hormone (GH) secretion is an important problem in pediatric endocrine practice. The diagnosis of GH insufficiency is based on the finding of a "blunted" GH response to GH provocative tests or on the demonstration of a decreased endogenous secretion. From a practical point of view, these methods are uncomfortable, expensive and time consuming. Recently, very sensitive specific assays to measure human GH in urine have been developed. We present a discussion of available data on these tests in order to estimate their role in the evaluation of a short or slowly growing child. The present available assays allow measuring very low levels of GH in a small sample of untreated urine. The main limitations of urinary GH measurement are the intrasubject variability, wide normal range, overlapping results in several GH secretory states and lack of information on GH pulsatility. However, most of these limitations also apply to other tests of GH secretion. The advantage of urinary GH tests is that they provide, in an easy procedure, information on serum GH concentration. There is good correlation between urinary and serum GH concentration and several findings suggest that urinary GH excretion reflects changes in plasma GH levels during the period of urine collection. Therefore, the usefulness of urinary GH measurement is that of a simpler and cheaper screening method for assessing integrated serum GH concentration in clinical practice.

Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis

Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis and to correlate these both to clinical and biochemical characteristics and survival rate. Urinary GH excretion, IGF-1, and other biochemical parameters were measured in 36 patients with alcoholic cirrhosis, while in the control group of 34 healthy individuals only U-GH excretion was measured. U-GH excretion was significantly higher in patients than in the healthy controls (p < 0.00001), and increased with deteriorating liver function assessed by modified Child-Turcotte score (p < 0.01). The highest U-GH excretions were found in patients with hepatic encephalopathy (p < 0.003). IGF-1 levels were reduced in cirrhosis and correlated with liver function (p < 0.001). Serum IGF-1 concentrations below 3.1 nmol/l were associated with a poor prognosis (p < 0.004). The elevated U-GH in patients with alcoholic cirrhosis may reflect high serum levels of GH due to increased pituitary secretion or decreased hepatic degradation of GH. In addition, the IGF-1 levels reflect the degree of hepatic insufficiency and, thus, seem to provide new prognostic information.

Urinary Growth Hormone Excretion in Diabetic Children: Relation to Nocturnal Course of Blood Glucose Levels

A potential relation was evaluated between nocturnal urinary growth hormone (GH) excretion as a parameter for integrated GH secretion and the course of blood glucose (BG) levels during night and morning hours. Twelve diabetic children aged 11.6 +/- 2.0 years (mean +/- SD), with diabetes duration 4.4 +/- 1.6 years, took part in the study. Urine for GH estimation by a highly sensitive EIA was collected from 24.00 to 07.00 h during a diabetic summer camp. BG was monitored at 24.00, 04.00 and 07.00 h. Mean nocturnal GH excretion measured from 158 collections was 5.6 +/- 5.1 ng/g creatinine, with a wide range of 0.36-36.6. Remarkable intra-individual variations were found between distinct nights. GH excretion correlated positively with BG levels at 07.00 h (p = 0.003) and with the increment of BG between 24.00 and 07.00 h (p = 0.002). Thus, endogenous variations in nocturnal GH levels may be involved in the day-to-day fluctuations in fasting BG in diabetic subjects.

Is growth hormone associated with diabetic retinopathy?

The role of growth hormone (GH) in the pathogenesis of diabetic retinopathy was evaluated in 150 patients with non-insulin-dependent diabetes mellitus by measuring urinary GH excretion using a highly sensitive enzyme immunoassay. Urinary GH excretion was not significantly different among diabetic patients without retinopathy (mean, 2.4 ng/day; range, <0.3–20.0 ng/day), with background retinopathy (2.7 ng/day; <0.3–22.0 ng/day), and with proliferative retinopathy (3.1 ng/day, 0.9–15.6 ng/day). These data suggest that GH does not play a role for the pathogenesis of diabetic retinopathy through the increased physiological secretion.

Autoantibodies to endogenous growth hormone in short children (the Wessex Growth Study).

Small stature is associated with low growth hormone secretion, but in most cases the reason is unknown. The commonest cause of hormone insufficiency is autoimmunity, and autoantibodies to hormones are often found where there is autoimmune disease of the corresponding gland. Displaceable growth hormone binding by the sera of 125 short (< 3rd centile) but otherwise normal school entrants was significantly higher (P < 0.05) than by the sera of 100 age-matched children of normal height (10th-90th centile), and binding in 21 (17%) of the small children exceeded the upper limit of 95% of the normal population. Furthermore, urinary growth hormone excretion was significantly lower in the small children (total overnight output 0.6-1.7 ng) compared with controls (1.5-3.7 ng) (P < 0.05) even when corrected for body surface area. Thus, growth hormone binding and growth hormone excretion discriminated between two groups of children selected only on the basis of height. The assay used for growth hormone binding was specific for IgG, suggesting that the binding factor was antibody. Autoimmunity merits further investigation as a basis for poor growth.

Direct Double Monoclonal Immunoradiometric Assay of Urinary Human Growth Hormone

Several reports indicate that urinary growth hormone (GH) excretion might reflect central release of the hormone, and that measurement of urinary GH shows promise in the investigation of physiological and pathological GH secretion. We have developed and evaluated a direct immunoradiometric assay (IRMA) in which two monoclonal antibodies are used to measure GH in the urine of children. The detection limit is approximately 0.018 pmol/L for a sample volume of 2 mL. Within- and between-run variations (CVs) were 5.6% and 14.2%, respectively. Analytical recovery and dilution experiments showed the specificity of the method for GH. In normal-stature prepubertal children ages 3-12 years, 24-h urinary GH excretion was 0.189 (SD 0.100) pmol and correlated well with the amount of GH in the first morning miction, which showed wide day-to-day variations. Like others, we found a strong correlation between GH concentrations in serum and urine during stimulation tests with GH-releasing hormone (somatoliberin) and (or) during physiological nocturnal secretion, confirming that urinary GH measurement may be of help in investigating patients (particularly young children) with diseases in which GH secretion is impaired.

Clinical usefulness of urinary growth hormone measurements in normal and short children according to different expressions of urinary growth hormone data.

To assess the clinical usefulness of urinary growth hormone (UGH) measurements, a UGH determination technique, including dialysis, ultrafiltration, and measurement by polyclonal-coated tube RIA, was established. Sixty-three short children were studied: 56 idiopathic growth retarded (37 prepubertal and 19 pubertal) and seven prepubertal with classic GH (growth hormone) deficiency. Forty-two healthy children (32 prepubertal and 10 pubertal) served as controls. Two groups of adults were studied: eight with active acromegaly and 11 healthy controls. UGH was measured in 24-h urine samples from all patients and controls. Mean +/- SD UGH excretion expressed as ng/24 h was significantly lower in the GH-deficient group compared with prepubertal growth-retarded and control children (p less than 0.01). No differences were found between UGH excreted by controls and by the growth-retarded groups. Pubertal children excreted significantly higher amounts of GH when UGH was expressed as ng/24 h (p less than 0.02 and p less than 0.03, respectively), but this difference disappeared when UGH was expressed as ng/g creatinine. UGH was significantly higher in acromegalic patients compared with adult controls (p less than 0.001). Differences between day, night, and 24-h UGH were studied in 23 children. UGH in night urine was significantly lower whether expressed as the total amount or as ng/g creatinine. The effect of recombinant hGH administration on UGH was studied in 13 children after 6 and 12 mo of treatment. UGH increased significantly under recombinant hGH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary excretion of human growth hormone in children with short stature: Correlation with pituitary secretion of human growth hormone

Thirty-five children with short-stature underwent insulin-loading and sleep tests for assessment of secretion of human growth hormone. Correlations between the levels of human growth hormone in the serum and urine during the tests were examined to elucidate the clinical significance of urinary human growth hormone levels in short children. The concentration and total amount of human growth hormone in the urine correlated significantly with the peak concentration of serum human growth hormone (r = 0.81, p less than 0.001 and r = 0.80, p less than 0.001, respectively) and the integrated concentration of human growth hormone (r = 0.85, p less than 0.001 and r = 0.85, p less than 0.001, respectively) in the insulin-loading test. The concentration and total amount of human growth hormone in the morning urine also correlated significantly with the peak concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.70, p less than 0.001, respectively) and the integrated concentration of serum human growth hormone (r = 0.80, p less than 0.001 and r = 0.72, p less than 0.001, respectively) in the sleep test. The concentration or total amount of human growth hormone in the urine differed significantly among children with human growth hormone deficiency, those with nonendocrine short stature, and those with normal stature (p less than 0.05). These data suggest that measurement of human growth hormone in the urine may be used to assess secretion of human growth hormone, serving as a screening test for human growth hormone deficiency in children.

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.

Relationship between urinary and serum growth hormone and pubertal status.

Urinary growth hormone (uGH) excretion and serum growth hormone concentrations have been compared in three groups of children. Group 1 consisted of 21 children who had had cranial irradiation as part of their treatment for acute lymphoblastic leukaemia; group 2, 18 normal children; and group 3, 12 boys with constitutional delay in growth and puberty who were in early puberty. Children in groups 1 and 2 each had a 24 hour serum growth hormone profile (sampling every 20 minutes) and concurrent urine collection. The 12 boys in group 3 had a total of 21 profiles (sampling every 15 minutes for 12 hours) and concurrent urine collections. In the prepubertal children (n = 17), in both groups 1 and 2, there was a significant correlation between mean serum growth hormone and total uGHng/g creatinine. There were also significant correlations between total uGHng/g creatinine and both peak serum growth hormone and mean amplitude of the pulses in the growth hormone profile. In the pubertal children (n = 22), in groups 1 and 2, whether combined or in separate groups, there was no significant correlation between total uGHng/g creatinine and mean serum growth hormone, peak serum growth hormone, or mean amplitude of the pulses in the growth hormone profile. In group 3 there were significant correlations between total uGHng/g creatinine and both the mean serum growth hormone and mean amplitude of the pulses in the profile. Therefore uGH estimations appear to correlate well with serum growth hormone profiles in children who are prepubertal or in early puberty, but not in those further advanced in pubertal development. These results may reflect a variation in the renal handling of growth hormone during pubertal development. uGH estimation may be an unreliable screening investigation for growth hormone sufficiency in mid to late puberty.

Twenty-four-hour plasma growth hormone (GH) profiles, urinary GH excretion, and plasma insulin-like growth factor-I and -II levels in prepubertal children with chronic renal insufficiency and severe growth retardation

We studied 24-h plasma GH profiles, maximal GH responses to arginine provocation and insulin-like growth factor-I (IGF-I) and IGF-II levels in plasma in 22 euthyroid prepubertal children (mean age, 9.5 yr) with chronic renal insufficiency (glomerular filtration rate, <20 mL/min-1.73 m2) and severe growth retardation [mean (±SD) height SD score (SDS), −2.8 (1.1)]. The 24-h GH profiles were analyzed using the Pulsar program. Girls had significantly higher 24-h GH secretion than boys (P < 0.004). Children with end-stage nephrotic syndrome had higher baseline GH levels and total area under the curve (AUCo) than patients with dysplastic kidneys (P < 0.05), while the area under the curve above baseline (AUCb) was similar in all types of renal diseases. The type of treatment (conservative, peritoneal, hemodialysis) did not significantly influence the 24-h GH secretion. No correlation was found between 24-h GH profiles and age, height SDS for chronological age, height velocity SDS for bone age, and weight for hei...

Urinary Growth Hormone Excretion During Puberty in Type 1 (Insulin‐dependent) Diabetes Mellitus

The excretion of urinary growth hormone was measured by a highly sensitive direct immunoradiometric assay in a cross-sectional study during puberty in 70 children with Type 1 (insulin-dependent) diabetes mellitus and 94 normal children. In normal children (n = 24) and diabetic children (n = 17) overnight urinary growth hormone excretion correlated significantly with the mean overnight plasma concentration (r = 0.70, p less than 0.001, and r = 0.70, p less than 0.001), indicating that urinary GH excretion reflects the circulating endogenous GH level. Overnight urinary growth hormone excretion increased during puberty. In normal and in diabetic children there was a peak in boys at genital stage 4 (both p less than 0.01), and in girls at breast stage 2 (both p less than 0.02). The diabetic children excreted more urinary growth hormone than the normal children at every pubertal stage. Excretion of albumin, retinol binding protein and N-acetyl-beta-D-glucosaminidase was measured in urine from 38 diabetic children. Urinary growth hormone correlated weakly with urinary albumin (r = 0.49, p less than 0.01), retinol binding protein (r = 0.42, p less than 0.01), and N-acetyl-beta-D-glucosaminidase (r = 0.43, p less than 0.01). Urinary GH excretion was not related to blood glucose control (HbA1) in boys (n = 31) or girls (n = 39). The measurement of urinary growth hormone provides an assessment of endogenous growth hormone during puberty in normal and diabetic children. However, caution must be exercised in interpreting urinary growth hormone data from diabetic patients with increased excretion of albumin and retinol binding protein.

Urinary Growth Hormone Excretion in 657 Healthy Children and Adults: Normal Values, Inter- and Intraindividual Variations

Urinary growth hormone (u-GH) excretion was measured in 547 healthy children and 110 adults by ELISA with a detection limit of 1.1 ng/l u-GH after prior concentration of the urine samples (20- to 30-fold). u-GH excretion values were significantly dependent on the pubertal stage (p less than 0.0001) with maximum values in Tanner stage 3 for girls and 4 for boys. This corresponded to a peak in u-GH excretion between 11.5-14.5 years in girls and 12.5-16 years in boys. Additionally, u-GH excretion in adults was significantly higher than in prepubertal children (p less than 0.001). The day/night ratio of u-GH excretion (pg/h) was significantly higher in females than in males (p less than 0.01). In Tanner stages 1-4, u-GH excretion during the day was lower than that at night, whereas the opposite was true in late puberty and in adult women. The interindividual variation of u-GH excretion within the same Tanner stage was considerable and approximately double the intraindividual variation. The day-to-day variation could be further reduced by collection of three consecutive urine samples. The variations were larger if night samples instead of 24-hour samples were considered. The expression of u-GH excretion in nanograms per gram creatinine did not diminish the observed variation and blunted the pubertal increase in u-GH excretion. In conclusion, (1) u-GH excretion depends significantly on age, sex and pubertal maturation as does the day/night ratio of u-GH excretion. (2) The interindividual variation in u-GH excretion is considerable.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in urinary growth hormone excretion in puberty.

During the pubertal years the overnight urinary excretion rate of growth hormone (hGHu) increases to three to four times the prepubertal rate, reaching a peak in girls at 13 years and in boys at 15 years. After puberty the mean rate of overnight hGHu is twice that before puberty.

Comparison of Urinary Growth Hormone and IGF-I Excretion in Small- and Appropriate-for-Gestational-Age Infants and Healthy Children

The output of urinary growth hormone (GH) and IGF-I were quantitated by RIA in 12-h urine collections obtained from infants who were preterm, small for gestational age (PT-SGA, n = 13); preterm, appropriate for gestational age (PT-AGA, n = 27); full term, small for gestational age (FT-SGA, n = 13); and full term, appropriate for gestational age (FT-AGA, n = 29); and from normal children (n = 33). The amounts of GH and IGF-I (mean +/- SEM) excreted by the PT-SGA and FT-SGA infants were not significantly lower than those excreted by the PT-AGA and FT-AGA groups, respectively [GH (micrograms/kg): PT-SGA 13.7 +/- 3.1 versus PT-AGA 14.0 +/- 2.2, FT-SGA 7.8 +/- 2.4 versus FT-AGA 6.6 +/- 1.8; IGF-I (nmol/kg): PT-SGA 0.52 +/- 0.09 versus PT-AGA 0.53 +/- 0.04, FT-SGA 0.31 +/- 0.05 versus FT-AGA 0.35 +/- 0.04]. All infant groups exhibited significantly greater outputs of urinary GH and IGF-I compared with the children (p less than 0.01). The plasma concentrations of GH in all infant groups were high, whereas the plasma IGF-I levels were low. Microalbumin and beta-2 microglobulin excretion did not correlate with urinary GH and IGF-I output. Despite the higher microalbumin output in FT babies, urinary GH and IGF-I excretion was lower in these groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of Activity in Postoperative Acromegalics Plasma Growth Hormone Levels during Oral Glucose Tolerance Test, Daytime Blood Sampling and Urinary GH Excretion.

Plasma growth hormone (GH) levels during oral glucose tolerance test (OGTT) and during the daytime (0900-1700 h) and urinary GH excretion were determined in 6 normal subjects and 10 patients with postoperative acromegaly by means of a highly sensitive enzyme immunoassay (EIA). Acromegalic patients were divided into two groups according to their GH responses during OGTT. In group I patients plasma GH was suppressed below 1.0 microgram/l as in normal subjects, whereas GH levels persisted above 1.0 microgram/l in group II patients. Plasma GH profiles during the daytime were characterized by low nadir GH levels in normal subjects (0.21 +/- 0.10 microgram/l and group I patients (0.38 +/- 0.10 microgram/l) when compared with those in group II patients (4.7 +/- 2.0 microgram/l). Nadir GH levels during the daytime coincided with those during OGTT. Urinary GH excretions in group I patients (median 12 ng/day, range 4.3-29 ng/day) were within normal limits (2.6-20 ng/day) and significantly lower than those in group II patients (median 40 ng/day, range 19-130 ng/day.) Determination of plasma GH levels during OGTT and urinary GH excretion by the highly sensitive enzyme immunoassay is useful in evaluating the activity of postoperative acromegaly.

Effect of Chronic Clonidine Treatment on Urinary Growth Hormone Excretion and Linear Growth in Children with Short Stature

Eleven prepubertal children with short stature were treated with clonidine (0.15 mg/m2 daily) for a period of 1 year. The effect of this drug was evaluated on both clinical (growth velocity, height standard deviation scores for chronological age and bone age) and hormonal (urinary growth hormone excretion and insulin-like growth factor I) parameters. Our study shows that long-term clonidine administration in children with short stature did not result in significant differences in growth velocity, height standard deviation scores for chronological age and bone age, insulin-like growth factor I or in urinary growth hormone excretion.

Urinary growth hormone excretion as a screening test for growth hormone deficiency.

Overnight urinary growth hormone secretion was measured by an immunoradiometric assay incorporating commercially available reagents, in 41 normal prepubertal school-children from three age groups: 3-5 years, 6-7 years, and 9-10 years. There was no significant difference between the groups expressing the results as total microU/specimen and so they have been combined to provide a prepubertal reference range of 2.25-10.50 microU/night. Prepubertal children with growth hormone deficiency who had not been receiving growth hormone treatment for two days had overnight urinary growth hormone concentrations well below this range. Urinary growth hormone was assayed in 49 children undergoing investigation for short stature with conventional provocative testing, and those shown to have growth hormone deficiency had correspondingly low overnight urinary growth hormone concentrations. There was, in addition, a strong correlation between overnight urinary growth hormone concentrations and peak serum response to provocation. This simple urine assay may provide a useful screening test for growth hormone deficiency.