Sm-C Concentrations Research Articles

Removal of Radioactive Cs Using Aqueous Sodium Metasilicate with Reduced Volumes of Waste Solution

Remediation of materials contaminated with a radioactive material such as 137Cs is important. Here, we report on the effectiveness of an aqueous sodium metasilicate prepared with a microbubble crushing process (SMC) for the removal of radioactive 137Cs from granule conglomerates and nonwoven cloth. A 137Cs removal ratio of 78% was achieved for the nonwoven cloth sample, and multiple washings at low SMC concentrations were effective. In addition, the volume of the waste solution could be reduced by neutralizing the SMC and using gelation to remove the radioactive material. The decontamination is shown to be more efficient than that with sodium hydroxide, even for washing granule conglomerates.

Effect of Chronic Clonidine Administration on GH Secretion in Adult Human Subjects

It is well known that the acute administration of clonidine, an alpha 2-adrenergic agonist commonly used as an antihypertensive drug, stimulates GH secretion, likely via hypothalamic growth hormone releasing hormone (GHRH) release. Conversely, evidences of a hyperactivity of GHRH-GH-somatomedin C (SMC) axis during chronical administration of clonidine are controversial. In this study, GH and SMC levels have been evaluated in 16 hypertensive patients chronically treated with clonidine. The subjects were randomized to receive either TRH or saline with the aim of evaluating the non specific GH response to TRH as compared to spontaneous fluctuations during a control test. In basal conditions, GH and SMC concentrations in clonidine treated patients were similar to those observed in an age and sex matched group of normal untreated subjects. An abnormal increase in plasma GH occurred in 5 out of the 10 patients who received TRH, while plasma GH did not show significant variations during testing in the subjects who received saline. It is suggested that chronical administration of clonidine does not induce an hyperactivity of GHRH-GH-SMC axis as estimated by plasma GH and SMC concentrations, but may induce a disorder in hypothalamic control of GH secretion, possibly implicated in the abnormal GH responsivity to TRH.

Somatomedin-C in Active and Successfully Treated Acromegaly

Sm-C concentrations in serum were found significantly different in either active acromegaly or following successful treatment with pituitary adenomectomy. Although after normalization of serum GH the Sm-C levels sometimes exceeded the normal range no overlap was found between both groups. Exceptionally two acromegalic patients showed elevated Sm-C levels in spite of normal GH values. Likewise, a high Sm-C concentration was found in one patient suspective of ectopic GH secretion with only moderately elevated serum GH. Sm-C determinations are judged as a good adjunct to usual diagnostic methods which in special cases of acromegaly can be even superior to measurements of serum GH.

Somatomedin-C in the kidney of streptozotocin diabetic rats.

To evaluate the possible role of somatomedin-C, insulin-like growth factor I, in renal hypertrophy in early diabetes, kidney tissue SmC concentrations were measured in streptozotocin-induced (80 mg/kg ip) diabetic rats. Body weight, liver weight, plasma SmC concentration, and SmC concentration in the liver of diabetic rats were significantly lower than those of controls. Seven days after induction of diabetes, the kidney weight (898 +/- 95 mg) in diabetic rats was significantly greater than that in controls (755 +/- 69 mg), while SmC concentration in the kidney of diabetic rats (1.7 +/- 0.3 U/g kidney) was significantly lower than that of control rats (5.4 +/- 0.6 U/g kidney). These results suggest that renal SmC may not have an important role in renal hypertrophy in early stages of diabetes and that renal production of SmC may be impaired by insulin deficiency in rats.

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.

Immunoreactive somatomedin C/insulin-like growth factor I in urine from normal subjects, pituitary dwarfs, and acromegalics.

Using antibodies to somatomedin C/insulin-like growth factor I (SmC) produced in rabbits using the recombinant hormone, we have developed a radioimmunoassay for SmC. Gel-chromatography of urine revealed that the vast majority of immunoreactive SmC was eluted coincident with 125I-SmC and a small portion eluted with fractions having a mol. wt. range of 30,000-40,000. The SmC concentration in urine was determined by radioimmunoassay after ammonium sulfate extraction. Values did not ordinarily exceed 1 ng/ml. When the values from normal subjects were expressed as ng/mg creatinine, high levels were observed in the neonatal period. These values fell rapidly in infancy, declined more gradually in childhood, were slightly elevated at early puberty, and were lowest in adulthood. Urine SmC concentrations in 15 pituitary dwarfs were lower than the averages obtained from agematched control subjects, and six of them showed abnormally low values. Three patients with active acromegaly had high SmC values in urine. In conclusion, 1) SmC, mainly of monomeric form, was immunologically detected in urine. 2) Radioimmunoassay for urine SmC revealed that values varied considerably with age in normal subjects and were partially dependent on the human growth hormone status. However, the full meaning of the findings remains to be elucidated.

ABSENCE OF ULTRADIAN RHYTHM OR DIURNAL VARIATION IN CIRCULATING SOMATOMEDIN-C (Sm-C) IN RATS

We studied the variation in plasma Sm-C in unrestrained, cannulated rats. Six rats were sampled every 15 min for 6 hr, and 5 rats were sampled every 2 hr for 36 hr. Plasma was assayed for Sm-C (RIA) before and after acid-ethanol extraction (AE), and for growth hormone (GH). AE increased the immunoreactivity of Sm-C in heparinized rat plasma and in freshly-collected serum 3-fold AE had no effect on serum stored at −20° C. >4 wks, which had comparable potency to AE serum and AE plasma. In rats sampled every 15 min, GH showed high amplitude, light entrained pulses every 3.3 ± 0.15 (SEM) hr. By visual inspection, there were no pulses of Sm-C. We further analyzed the data with 2 computer algorithms designed to detect hormone pulses. Of the 5 Sm-C pulses identified by both programs in unextracted plasma, only 1 was also identified in the corresponding AE plasma. When both pulse detection methods were applied to the data from both unextracted and AE plasma from all 6 rats, no pulses were identified in 10 of the 24 series of measurements. In 19 identical dilutions of a single serum sample, one program identified 2 “pulses,” and the other, none. In rats sampled every 2 hr for 36 hr, there was no episodic fluctuation of Sm-C. Thus, there is little evidence for episodic release of Sm-C into blood, either as pulsations entrained to light or to feeding cycles. Sm-C measurements made on single blood samples from normal animals reliably reflect Sm-C concentrations over the course of 24 hr.

Effect of thyroid hormone therapy on plasma insulin-like growth factor I levels in normal subjects, hypothyroid patients and endemic cretins.

The effect of thyroid hormone therapy (L-T4 or L-T3) on plasma immunoreactive insulin-like growth factor I (somatomedin C, Sm-C) concentrations was studied in 8 normal controls, 14 primary hypothyroid subjects and in 7 patients with endemic cretinism. In normals basal levels of Sm-C (1.56 +/- 0.77 U/ml) increased to (2.46 +/- 1.0 U/ml; L-T4) and to (2.9 +/- 0.95 U/ml; L-T3). Plasma Sm-C basal levels were significantly lower in primary hypothyroid subjects (0.81 +/- 0.48 U/ml) and increased to 2.54 +/- 1.43 U/ml (L-T4) and to 2.16 +/- 0.83 U/ml (L-T3). A significant and positive correlation (r = 0.56) was found between Sm-C and serum T4 and T3 concentrations. Plasma Sm-C concentrations in endemic cretinism were initially normal in 4 patients, but low in the remaining 3 (mean +/- SD: 1.18 +/- 0.63 U/ml) and did not increase after 12 months (1.34 +/- 0.61 U/ml) or 18 months (1.01 +/- 0.43 U/ml) of L-T4 and L-T3 therapy. Plasma T4 levels and free T4 increased considerably in EC after therapy with a significant decrease in the previously elevated plasma TSH concentrations. The subnormal response of plasma Sm-C during effective thyroid thyroid hormone therapy could be an additional factor involved in growth failure of endemic cretins.

Puberty in the chimpanzee: somatomedin-C and its relationship to somatic growth and steroid hormone concentrations.

A relationship between sex steroids and the somatomedins (Sms) is well known, but poorly defined. In some primates, including man, there are pubertal increases in Sms, concurrent with increased growth and sex steroid production. In the current studies, indices of somatic growth [body weight, crown-rump length (CRL), and testis size (testicular volume index)] and circulating concentrations of testosterone (T), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), cortisol, and Sm-C were determined (n = 208) in 86 male and female chimpanzees during a 1-yr period. In addition, we have attempted to determine whether plasma Sm-C concentrations correlate with serum levels of estrogen and androgens. In male animals between 6 and 8 yr of age, there was a marked increase in testicular size, concurrent with an increase in serum T and preceding slightly an increase in the rate of body weight gain. There were no detectable increases in serum E2 or the CRL slope. In females between 6 and 8 yr of age, serum T increased, concurrent with an increase in the rate of body weight gain much smaller than that in male animals. Serum E2 increased only after 10 yr of age, and no increased linear growth (CRL) was found. In both sexes, increases in serum DHEA-S were found by 4-6 yr of age, in contrast to cortisol concentrations, which were high and remained unchanged from birth to 12 yr of age, except for lower values in the very youngest and very oldest female animals. An increase in Sm-C occurred in both sexes by 4-6 yr of age, with higher values in female than in male animals 0-2, 4-6, and 6-8 yr of age, and when all ages were considered together. In both sexes, plasma Sm-C concentrations correlated with serum T (r = 0.60 and P less than 0.001; r = 0.68 and P less than 0.001; females and males, respectively), although when both sexes were analyzed together, the correlation was not as good (r = 0.36; P less than 0.001). Sm-C concentrations correlated with serum DHEA-S when the two sexes were analyzed separately (r = 0.44 and P less than 0.001; r = 0.54 and P less than 0.001; females and males, respectively) or together (r = 0.49; P less than 0.001). Sm-C correlated poorly with serum E2 levels in females (r = 0.20; P less than 0.05) and did not correlate with E2 in males.(ABSTRACT TRUNCATED AT 400 WORDS)

92 LOW SERUM SOHAT0MEDIN-C (SM-C) IN INSULIN-DEPENDENT DIABETES: EVIDENCE FOR A POST-RECEPTOR DEFECT

In poorly controlled insulin-dependent diabetes, serum Sm-C concentrations are low despite high levels of growth hormone (GH), suggesting GH resistance. Whether this resistance might be due to receptor or post-receptor defects remains however unclear. Therefore, the number and affinity constant of liver bovine GH binding sites and the serum Sm-C concentrations, 24 h after injection of graded doses of GH, were determined in hypophysectomized rats injected with saline (controls) or with 40 mg of streptozotocin/kg BW (diabetics). After one week of diabetes there were no significant changes in the affinity constants (diabetics : 0.68 ± 0.04 × 109 M−1 vs controls : 0.92 ± 0.07 × 109M−1 ; mean ± SE; n=8; P < 0.1) or the numbers of GH binding sites (diabetics : 1.10 ± 0.12 pmol/mg DNA vs controls : 1.26 ± 0.15 pmol/mg DNA; P < 0.5). Despite the absence of alterations in GH binding, the maximal serum Sm-C response was severely blunted in the diabetics (2.02 ± 0.32 U/ml) when compared to controls (17.41 ± 2.69 U/ml; P < 0.01). The sensitivity (ie ED50) however was the same for control and diabetics rats.

464 TESTOSTERONE (T) BUT NOT OXANDROLONE (OX) INCREASES SPONTANEOUS GROWTH HORMONE (GH) AND SOMATOMEDIN-C (SmC) CONCENTRATIONS IN BOYS WITH CONSTITUTIONAL DELAY OF GROWTH AND ADOLESCENCE (CDGA)

The effect of T and OX on GH and SmC concentrations was studied in boys with CDGA. Ten boys received OX (0.1 mg/kg/d) for 65±5 d and 5 boys received T propionate (7.5 mg IM × 7 d) followed by T enanthate (100 mg IM q mo for 3 mo). Serum GH was measured in samples obtained q 20 min for 24 hr before and 65±5 d into therapy. SmC levels were measured twice during the same 24 hr period before and 65±5 d into therapy. The 24 hr integrated concentration of GH (ICGH) was obtained from the mean of 72 samples and compared to that obtained from a pooled sample (p=NS). A pulse of GH was recorded if the peak level rose >5 ng/ml. We found no differences in the ICGH, in the number of GH secretory episodes, or in the SmC levels in boys treated with OX. However, in boys treated with T there were significant increases in the ICGH, the number of GH secretory episodes and in the SmC levels.We conclude that testerone therapy doubles the amount of GH secreted daily, although OX at 0.1 mg/kg/d is without effect. This increase in GH secretion may contribute to the increased growth rate at puberty.

301 SOMATOMEDIN-C (SM-C) LEVELS IN FETAL SHEEP ARE INDEPENDENT OF SERUM PLACENTAL LACTOGEN LEVELS

The factor(s) regulating fetal growth remain obscure and classic hormones appear not to be involved. Fetal size correlates with fetal SM-C levels; however, fetal growth hormone appears to have no effect either on fetal SM-C or fetal growth. Placental lactogen has been suggested as a modulator of fetal somatomedins. To assess this possibility in the sheep model, time-dated pregnant ewes with singleton fetuses (n=7) underwent fetal arterial catheterization at 111±3 d of gestation (term=150 d). Daily blood samples were obtained from each fetus until parturition or death. (Mean survival=20 d). Serum samples were assayed for both placental lactogen and SM-C. There was no correlation between placental lactogen and SM-C during the study period (r=.03, n=82). A second group of fetuses (n=5) underwent single umbilical artery ligation at 111±3 d of gestation. This procedure results in markedly elevated levels of placental lactogen in the fetus. Chronically catheterized animals were sampled daily and samples were assayed for both placental lactogen and SM-C. Despite the increased plasma placental lactogen levels in these single umbilical artery ligated fetuses, there was no demonstrable correlation between plasma placental lactogen and SM-C concentrations (r=.03, n=66).Conclusion: Somatomedin-C levels in fetal sheep are independent of serum placental lactogen levels during the third trimester.

501 SOMATOMEDIN (Sm-C) in FETAL GROWTH

In the postnatal rat, suboptimal nutrition leads to a decrease in Sm-C which may account for the resultant decrease in growth. To study the effect of fetal malnutrition on serum and tissue Sm-C concentrations, intrauterine growth retardation(IUGR) was induced by uterine artery ligation on day 17 of gestation in 15 pregnant rats. Fetuses of the non-ligated horns served as appropriately grown(AGA) controls. After surgery the animals were allowed ad libitum feeding. On day 21 fetal blood and organs were obtained and analyzed for Sm-C and insulin by radioimmunoassay and glucose by glucose oxidase. Data are presented in relation to uterine position with 1 denoting the fetus nearest the ovarian artery. At each position, IUGR fetuses had decreased weight, serum and liver Sm-C, glucose, and insulin concentrations. (x±sem, *p<.05) Fetal weight was significantly related to glucose (r=.730), liver Sm-C (r=.682) and serum Sm-C (r=.452). Stepwise linear regression demonstrated that these three factors in combination correlated highly with fetal weight (r=.836). A weaker correlation existed for insulin (r=.378) and lung Sm-C (r=.209). These data indicate that, in the fetus, Sm-C is influenced by nutrition and may have a mediating role in the control of growth.

474 ACUTE GROWTH HORMONE (GH) ADMINISTRATION: EFFECTS ON SOMATOMEDIN-C (SM-C) AND THE SECRETORY RESPONSE TO GROWTH HORMONE RELEASING FACTOR (GRF) AND CLONIDINE

Studies in vitro, in animals, and in adults have suggested that SM-C, operating at both CNS and pituitary levels, mediates a feedback inhibition of GH secretion. To test this hypothesis in children we studied 11 short (height < 3rd%) boys, ages 7-14 with delayed bone ages and normal GH responses to standard tests. On successive days 2-hour clonidine (5ug/kg,p.o.) and GRF (0.3ug/kg, i.v.) tests were performed in the fasting state. Daily GH (0.1 U/kg, i.m.) was then given with a repeat clonidine test 20 h after the second dose and a GRF test 20 h after the third.Results are shown below:*Differs from baseline, p<0.05Pre-treatment with GH thus strongly inhibited the GH response to clonidine and GRF, acting at the hypothalamus and pituitary respectively. Although SM-C rose sharply, individual rises did not correlate with suppression of the GH response to clonidine (r=0.35;p=0.3) or GRF (r=-.05).Conclusion: inhibition by GH of its own secretion operates, at least in part, at the pituitary level. While the inhibition may be modulated by SM-C, its extent does not depend directly on plasma SM-C concentrations.

Relationship of somatomedin-C concentrations to pubertal changes

The plasma somatomedin-C concentration increases above adult values during the teenage years. We studied the relationship of pubertal variables and the adolescent growth spurt to the changes in plasma total Sm-C concentration in normal volunteers and in boys with delayed puberty. The rise in plasma Sm-C concentrations was gradual and correlated positively with pubertal variables rather than with age. By midpuberty, plasma Sm-C had usually risen twofold. The Sm-C level in midpubertal girls (3.1 +/- 1.1, SD, U/ml) was greater than that in midpubertal boys (1.9 +/- 0.50, P less than 0.05). The Sm-C concentration in sexually mature teenagers was two to three times greater than that of adults. Both estrogens and androgens correlated independently with the plasma Sm-C concentration. The data are compatible with the hypothesis that pubertal estrogen or testosterone levels cause an increase in Sm-C, an effect possibly mediated by stimulation of growth hormone secretion, whereas greater estrogen exposure inhibits Sm-C generation, possibly by a direct effect. Plasma Sm-C concentrations correlated significantly with linear growth velocity until the age of peak pubertal growth velocity. Maximum Sm-C values were observed after the peak pubertal growth velocity was achieved, as height velocity was decelerating, and remained above adult levels for at least two to six years, at which time linear growth had virtually ceased. In boys with delayed puberty, Sm-C values resembled those of boys of like pubertal stage more closely than those of boys of similar age. Depressed plasma Sm-C values were found in some boys with delayed puberty; however, these did not preclude subsequent normal linear growth during sexual maturation.

Plasma somatomedin-C during the first year of life

THE SOMATOMEDINS are believed to mediate the growth-promoting effects of growth hormone. Although their concentrations in blood are low in hypopituitary children and increase after growth hormone administration, a convincing correlation between somatomedin and growth velocity has not been demonstrated in normal prepubertal children. Indeed, despite the rapid rate of growth in the perinatal period, somatomedin concentrations in cord blood are lower than in children and adults. 1 Based on limited numbers of determinations in a variety of assays, it appears that blood somatomedin values remain low during the first two year s of life, 2'3 a period during which growth velocity falls sharply; however, no longitudinal data have been reported. We have determined by radioimmunoassay the levels of one of the somatomedins, somatomedin-C, in normal infants during the first year of life and investigated whether Sm-C concentrations obtained serially correlate with changes in growth rate during this period. MATERIALS AND METHODS

Growth and somatomedin-C responses to growth hormone in dwarfed children

Nineteen children were studied because of short stature. They had in common abnormally low Sm-C values for age, and each received a ten-day course of exogenous GH therapy. Based on their endogenous GH concentrations and the response to GH therapy, in terms of Sm-C and height increments, they were classified into three groups. Group I included patients with GH insufficiency who had blunted GH responses to stimulation, but responded to therapy by normalizing the Sm-C concentration and velocity of growth. Group II patients all had normal GH responses to stimulation, but their responses to exogenous GH were similar to those observed in the GH deficient subjects. In the two children in Group III who had normal release of endogenous GH, Sm-C values and growth rate did not increase in response to GH. Group II patients may represent children with biologically inactive but immunoreactive GH, whereas the children in Group III are examples of the Laron type of dwarfism. Thus, rather than the plasma GH response to provocative stimuli, the Sm-C and growth increment responses to short-term exogenous GH therapy may more precisely identify children that will benefit from long-term GH therapy.

The use of a commercially available somatomedin-C radioimmunoassay in patients with disorders of growth

Somatomedin-C concentrations were measured by a newly available commercial radioimmunoassay in plasma samples from 41 children undergoing clinical evaluation of hypothalamic-pituitary function because of varied disorders of growth. Sequential Sm-C levels were stable; the coefficient of variation remained below 10% over a three-hour period. The Sm-C values of 27% of the children were discordant with the GH responses; of 25 patients with normal provoked-GH levels, seven had low Sm-C values, whereas four of 16 patients with inadequate GH responses had normal Sm-C concentrations. All of the discordant data occurred in 31 patients with diminished linear growth velocity. More patients with decreased growth velocity had diminished Sm-C levels than did short children with normal linear growth velocity. These data suggest that many variables, in addition to adequacy of GH production and plasma Sm-C levels, may affect net Sm-C activity. This possibly reduces the usefulness of the Sm-C radioimmunoassay as a single screening test for abnormalities of GH secretion.

Effect of pubertal stage and recent blood glucose control on plasma somatomedin C in children with insulin-dependent diabetes mellitus.

One hundred and fifty-five children with insulin-dependent diabetes mellitus were studied to determine the relationship of plasma somatomedin C concentrations to pubertal stage, recent blood glucose control, duration of diabetes, and daily insulin dosage. Plasma somatomedin C, as measured by radioimmunoassay, increased with age and the progression of puberty in both boys and girls, but was not different from those of normal children aged 5–18 yr. In diabetic children under 5 yr of age, plasma somatomedin was significantly lower than in normal children. These results are different from those reported previously in diabetic children, in which somatomedin activity was measured using a pig cartilage bioassay. In boys, puberty was accompanied by an increase in hemoglobin A1c from 11.6 to 14.1% despite a 36–44% increase in total daily insulin dosage adjusted for body weight. In girls, puberty was also associated with an increase in hemoglobin A1c (12.1–15.1%) without a change in weight-adjusted insulin dose. Although there was no apparent correlation between hemoglobin A1c and somatomedin C in the group as a whole (r = −0.078), multiple regression analyses demonstrated a significant negative correlation between these two variables (P &amp;lt; 0.001) when considered independently of age, sex, pubertal stage, duration of diabetes, and insulin dose. Pubertal status had a significant (P &amp;lt; 0.01) effect on plasma somatomedin C; plasma somatomedin C was also significantly positively correlated with the duration of diabetes (P &amp;lt; 0.01) but not with weight adjusted insulin dose. SMC concentration was not correlated with age when this variable was considered independently of puberty (P = 0.26). The data indicate that puberty and metabolic control both have significant yet independent effects on somatomedin C in children with insulin-dependent diabetes. In addition, the increased somatomedin C associated with puberty may contribute to the accelerated development of diabetic complications seen at this time, while the lowering of somatomedin C associated with worsening metabolic control may adversely affect linear growth.

443 DIURNAL VARIATION IN PLASMA CONCENTRATIONS OF SOMATOMEDIN C (SmC) IN CHILDREN

In order to determine if plasma SmC levels fluctuate, this peptide was measured (Nichols Institute, San Pedro, CA) at 12 hour intervals (9-10 am,9-10 pm) for 12-48 hours in 18 children (12 boys, 6 girls; 3-18 years) without organic endocrine dysfunction. At consecutive 12 hour intervals [SmC] were: In this population the mean evening concentration of SmC (0.67 ±.06 U/ml; N=22) was significantly (p <0.01) higher than the morning SmC value (0.46 ±.04 U/ml; N=37). In children with psychosocial deprivation or constitutional delay in growth and development associated with suboptimal nutrition, morning concentrations of SmC were often low, while evening values were normal. In two GH deficient children and one with bioinactive GH, SmC concentrations were low at all times. Diurnal variation in SmC concentrations was not observed in patients with gonadal dysgenesis (N=2) and hypogonadotropic hypogonadism (N=2). Conclusions: 1) There is a diurnal variation in plasma concentrations of SmC; SmC levels are higher at night than in the morning; 2) The diurnal variablity in SmC values may be useful in distinguishing patients with low SmC concentrations not due to hypopituitarism from children with GH deficiency.