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Biomedical subjects

S L Blethen

Publications and source records attributed to S L Blethen.

At least 73 records · Page 4Linked to original sources
PubMed1985

Modulation of glucocorticoid secretion by growth hormone.

We measured the cortisol and corticosterone responses to insulin-induced hypoglycemia in 13 growth hormone (GH)-deficient children and 30 short children without GH deficiency. Although there was no difference between the two groups in degree of hypoglycemia attained, baseline cortisol, baseline corticosterone, or cortisol 40 min after insulin injection, GH-deficient children had a significantly greater corticosterone response to this stress (3.6 +/- 0.4 versus 1.9 +/- 0.2 micrograms/dl). (All data are presented as mean +/- SEM.) In order to explore the effect of GH on corticosterone secretion, we measured cortisol and corticosterone responses to synthetic (1-24) ACTH before and after 3 days of exogenous GH (0.2 unit/kg/day). In 13 GH-deficient children, GH treatment caused a significant decrease in the corticosterone response to ACTH (2.2 +/- 0.2 micrograms/dl before GH to 1.6 +/- 0.2 micrograms/dl; t = 5.22, p less than 0.001; paired t test) despite the fact that there was no significant change in the cortisol response to ACTH (18 +/- 2 micrograms/dl before and 16 +/- 2 micrograms/dl after). When seven short children who were not GH deficient underwent a similar 3-day course of GH, the decrease in their corticosterone response was much less although still statistically significant (2.0 +/- 0.5 to 1.8 +/- 0.5 micrograms/dl; paired t test, p less than 0.05). Again, the stimulated levels of cortisol were not affected by GH treatment (19 +/- 4 versus 18 +/- 3 micrograms/dl) These results indicate that GH modulates the adrenal response to ACTH by suppressing corticosterone secretion without affecting cortisol secretion. In summary, this study presents two new findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

17-Hydroxyprogesterone responses to adrenocorticotropin in children with premature adrenarche.

The adrenal secretory response to an iv bolus dose of ACTH was measured in 10 girls (4-8 yr of age), 5 boys (4-9 yr) with premature adrenarche (PA), and 20 normal children. The evening before the ACTH test, each subject took dexamethasone (1 mg at bedtime) to suppress the early morning surge of ACTH. The next morning, 2 serum samples were obtained before the administration of ACTH (Cortrosyn; 0.25 mg), and 2 samples were collected 30 and 45 min after ACTH administration. All samples were assayed for cortisol, dehydroepiandrosterone (DHEA), DHEA sulfate, 17-hydroxyprogesterone (17-OHP), and androstenedione. There was no significant difference in the dexamethasone-suppressed steroid levels between the children with PA and the normal children. After ACTH injection, cortisol, DHEA, 17-OHP, and androstenedione increased significantly. There was no significant change in DHEA sulfate. The mean 17-OHP response to ACTH in girls with PA was significantly higher than that in girls and women whose pubertal development was normal. This response was similar in magnitude to that in a group (n = 5) of obligate heterozygotes for congenital adrenal hyperplasia (CAH). These data suggest that many girls with PA have a mild adrenal steroid secretory defect that resembles the response in adult obligate heterozygotes for CAH due to 21-hydroxylase deficiency. In contrast to the girls, none of the boys with PA had an exaggerated 17-OHP response to ACTH. Thus, these boys had no evidence for an adrenal steroid secretory defect. In summary, although the clinical presentation of boys with PA is similar to that of girls with PA, there is a significant difference in the adrenal steroid secretory response to ACTH. Thus, the biochemical events that cause PA in boys may be different from the corresponding events in girls.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Somatomedin C response to growth hormone in psychosocial growth retardation.

Three children with psychosocial growth retardation increased their serum somatomedin C levels from 0.20 +/- .02 to 0.81 +/- 0.2 U/ml in response to exogenous growth hormone. The pattern of somatomedin C response to growth hormone was no different from that seen in 11 prepubertal children with growth hormone deficiency who received growth hormone according to the same acute treatment regimen. This result suggests that the poor growth response of children with psychosocial growth retardation to exogenous growth hormone is not due to an inability to synthesize somatomedin C, and that it may represent a degree of resistance to the actions of somatomedin C.

Child↗
PubMed1984

Comparison of predicted and adult heights in short boys: effect of androgen therapy.

We evaluated the accuracy of height predictions based on the tables of Bayley and Pinneau (2) in 43 boys with short stature. Sixteen boys were treated with androgens and 27 received no treatment. In 17 boys whose bone ages were within normal limits, and who received no treatment, the mean +/- SE predicted height of 164.9 +/- 1.5 cm was not significantly different from the mean adult height (166.5 +/- 1.5 cm). The predicted height exceeded the actual adult height by more than 5.1 cm in only one instance [5.1 cm is the degree of accuracy reported by Bayley and Pinneau (2)]. In 10 boys, whose bone ages were severely delayed (more than 2 SD below their chronologic age) and also were not treated, predicted height overestimated adult height by more than 5.1 cm in five of them. This difference was statistically significant (P less than 0.05). In five boys with normal bone ages, androgen therapy had no significant effect on either predicted height (168.1 +/- 4.1 before, 166.8 +/- 4.4 cm after) or actual adult height (166.5 +/- 4.1 cm). The 11 boys with severely delayed bone ages had a significant increase in predicted height during androgen therapy (165.4 +/- 1.5 to 169.8 +/- 1.7 cm, P less than 0.01), but actual adult height (162.4 +/- 2.4 cm) was not significantly greater than pretreatment predicted height. Further, the number of boys whose predicted height exceeded their adult height by 5.1 cm was not significantly different in treated (4/11) or untreated (5/10) boys.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1984

An improved method for evaluating testosterone biosynthetic defects.

A double-label, double-substrate incubation technique has been developed and used to study the conversion of progesterone to testosterone in testes extracts from incompletely virilized males. The procedure involves separation of the microsomes from a testicular homogenate, incubating the microsomes with 1 microM [7-3H] progesterone, 1 microM 17-hydroxy[4-14C]progesterone, and 0.25 mM NADPH in pH 7.4 phosphate buffer at 37 degrees C. Steroid precursors and products are separated by column chromatography on Sephadex LH-20 with a solvent system of isoctane:ethyl acetate:methanol (4:1:1 by volume). These procedures can be completed in 2 days, and thus the method represents an improvement in time, reproducibility, and simplicity when compared to techniques based on thin layer or paper chromatography. The method has been used to distinguish the biochemical abnormality in three cases with XY sex chromatin, posterior labial fusion, clitoromegaly, and hypospadias. The abnormalities identified were: Case 1, no defect in testosterone synthesis (probable androgen insensitivity); Case 2, 17-ketosteroid reductase deficiency; and Case 3, steroid-17, 20-lyase deficiency.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

The endocrine evaluation of three children with vasomotor flushes following hypothalamic surgery.

Although vasomotor instability or hot flushes are a well-known occurrence in women with natural or artificially-induced menopause, they have not previously been described in children. We report three children in different stages of puberty who developed vasomotor instability following surgery involving the hypothalamic-pituitary region. One, a 16 7/12 year old female with Tanner III breast development, had low oestradiol levels both pre- and post-operatively, but developed vasomotor symptoms only in the post-operative period. The second, a 12 4/12 year old boy, was sexually mature and had normal male levels of testosterone and total oestrogen when he developed hot flushes post-operatively. The third case, a boy, was prepubertal at the time of craniopharyngioma resection. Our results support the conclusion that neither oestrogen deficiency nor gonadotrophin excess are absolute requirements for the development of hot flushes. It is possible that either pressure-related factors or actual manipulation of the hypothalamic-pituitary region result in biochemical changes which result in the development of post-operative vasomotor instability in these children.

Adolescent↗
PubMed1983

Effect of in vitro action of serum proteases or exposure to acid on measurable immunoreactive somatomedin-C in serum.

The proportion of immunoreactive somatomedin-C (IR-Sm-C) in blood that is available for measurement in the RIA is influenced by whether the sample is processed as serum or plasma, by how promptly the sample is chilled and frozen, by whether the reaction is carried out in glass or polystyrene tubes and by whether the incubation mixture contains protamine or heparin. Although protamine buffers and polystyrene tubes increase the availability of purified somatomedin-C (Sm-C), they decrease the detectability of Sm-C in serum. By incubating serum at neutral or acid pH, this IR-Sm-C can be made available for measurement, suggesting that incubation alters the nature of the linkage between Sm-C and its binding proteins or causes a conformational change in the binding protein, resulting in greater exposure of IR-Sm-C. The increment in measurable IR-Sm-C that occurs at neutral pH appears to be due to the action of proteolytic enzymes since it is time, temperature, and pH dependent and is inhibited by a variety of protease inhibitors and chelating agents. The increment which occurs at acid pH is not inhibited by chelating agents or elevated temperature and must be due in part to acid hydrolysis of Sm-C and its binding proteins. However, since the acid-induced increment is optimal within a narrow pH range and falls off sharply below pH 3.5, acid proteases may also be involved. These observations, which provide insight into the nature of the serum proteins with which Sm-C is associated, bear on the interpretation of results of serum somatomedin measurements carried out with different methods. They also may aid in delineating the mechanisms by which the somatomedin contained in the macromolecular complex in serum is made available to tissues.

Adolescent↗
PubMed1983

Somatomedin binding proteins in GH-deficient children with normal plasma somatomedin levels.

The major portion of circulating somatomedin (SM) is specifically carried by a large molecular weight binding protein of 150,000 (150K BP). There also exists a species of unsaturated binding protein in plasma of 40,000 mol wt that binds radiolabeled SM more avidly than the 150K complex. Patients with GH deficiency appear to have higher levels of this smaller BP while exhibiting decreased tracer binding and endogenous SM in the region of the 150K BP when compared to normals. This suggests the GH dependence of the 150K BP. We report studies on four GH-deficient children who had normal growth and normal SM levels after intracranial surgery. All were hyperphagic and obese at the time of study and were on replacement medications with the exception of GH. Endocrine evaluation revealed mild hyperprolactinemia in three patients and high insulin levels in three. SM-C/insulin-like growth factor I (IGF-I) levels by RIA and IGF-II by radioreceptor assay were normal for age. Sephacryl-200 column chromatography on plasma samples from these patients revealed patterns of tracer binding and endogenous SM migration similar to those of normal and GH-treated hypopituitary patients. The chromatograms were different from those usually seen in untreated GH-deficient patients. SM binding in whole serum was also similar to that observed in normal children (38 +/- 7% [125I]IGF-II bound for patients compared to 39 +/- 3% for controls) and less than that observed in GH-deficient children (48 +/- 5%). These data suggest that the characteristics of SM binding in our patients are similar to those of normal subjects. The regulation of the 150K BP is not accomplished by GH in these patients, although the exact mechanism for the maintenance of serum SM is unclear.

Adolescent↗
PubMed1983

Use of a two-site immunoradiometric assay for growth hormone (GH) in identifying children with GH-dependent growth failure.

Children with GH-dependent growth failure have normal GH responses to provocative stimuli, but, nonetheless, show increased growth rates when treated with replacement doses of human GH. We studied the GH secreted by 8 such children using a 2-site immunoradiometric assay for GH (IRMA-GH). To be detected in this assay, a GH molecule must be able to react simultaneously with two different monoclonal antibodies, each specific for a different region of the GH molecule. We compared the GH values observed in the IRMA to those obtained using classical RIA for GH (RIA-GH). The IRMA-GH to RIA-GH ratio was not affected by time of sample collection relative to peak GH serum levels in either normal individuals or children with GH-dependent growth failure. The ratios in serum samples from children with GH-dependent growth failure were significantly lower than those observed in normal individuals [0.35 +/- 0.005 vs. 0.48 +/- 0.02 (+/- SE); P less than 0.001]. All of the children with GH-dependent growth failure had IRMA-GH to RIA-GH ratios less than 0.4, while only 7 of 24 normal individuals had ratios this low (P less than 0.005). We suggest that a comparison of IRMA-GH with RIA-GH may supplement other clinical measurements and aid in identifying children with GH-dependent growth failure.

Adult↗
PubMed1982

Kinetics of the somatomedin C/insulin-like growth factor I: response to exogenous growth hormone (GH) in GH-deficient children.

The somatomedin C/insulin-like growth factor I (SMC/IGF-I) response to human GH (hGH) therapy and the t1/2 of SMC/IGF-I after the cessation of hGH were determined in 15 children with GH deficiency. After 5 injections of hGH (0.1 U/kg), there was a significant increase in total SMC/IGF-I [from 0.27 +/- 0.06 to 1.19 +/- 0.17 U/ml (mean +/- SEM)]. Both the pretreatment SMC/IGF-I and the maximal SMC/IGF-I levels attained were correlated with chronological age and bone age. Body size, as indicated by height and weight, also correlated with pretreatment and maximal SMC/IGF-I levels. For both pretreatment and maximal SMC/IGF-I levels, there was a better correlation of SMC/IGF-I levels with bone age than with chronological age. While the correlation between height and the pretreatment SMC/IGF-I level was stronger, weight was a better predicter of the maximal SMC/IGF-I level. Maximal SMC/IGF-I levels were reached 18.8 +/- 2.9 h after the last hGH injection. The t1/2 for SMC-IGF-I after the attainment of maximal levels was 20.7 +/- 2.3 h, or 39.5 +/- 3.8 h from the last injection of hGH. The t1/2 of SMC/IGF-I determined in this way was longer than previous values reported from studies in the rat. The relatively long t1/2 of SMC/IGF-I which we observed may in part explain the success of present GH treatment regimens which involve every other day injections of hGH.

Adolescent↗
PubMed1981

Plasma somatomedins, endogenous insulin secretion, and growth in transient neonatal diabetes mellitus.

Infants with transient neonatal diabetes mellitus are small for gestational age and fail to thrive postnatally unless insulin is administered. We have measured the concentrations of insulin-related growth factors in an infant girl with this condition to learn if deficiencies in one or more of these factors could be responsible for the impaired growth. Cord blood serum radioimmunoassayable insulin and somatomedin C/insulin-like growth factor I (SMC/IGF-I) were low, but insulin-like growth factor II (IGF-II) measured by a specific radioreceptor assay was normal. Insulin therapy begun on the fourth day of life resulted in a prompt increase in weight and a delayed rise in SMC/IFG-I. No significant changes in IGF-II were observed. After 2.5 months, insulin treatment was discontinued. At that time, endogenous insulin secretion was documented by increased urinary C-peptide. Normal growth and SMC/IFG-I levels persisted. We conclude that growth failure in this condition may be related not only to a lack of insulin but also to SMC/IGF-I deficiency. A deficiency in IGF-II is not involved.

Adult↗
PubMed1981

Plasma somatomedins in children with hyperinsulinism.

Hyperinsulinism has been postulated as a possible stimulus to somatomedin (SM) synthesis by the perfused rat liver and in man. Seven children who presented with severe fasting hypoglycemia and who had documented hyperinsulinism were studied to explore the effect of excessive endogenous insulin secretion on plasma levels of the SMs. Neither the concentration of somatomedin C/insulin-like growth factor-I (SMC/IGF-I) (mean +/- SD, 0.53 +/- 0.37 U/ml) nor that of IGF-II (1.10 +/- 0.58 microgram/ml) was significantly different from values observed in normal children. SMC/IGF-I and IGF-II were inversely correlated. There was a positive correlation between SMC/IGF-I and body weight, and an inverse correlation among IGF-II, body weight, and length. These results suggest that in children with normal GH secretion, hyperinsulinism sufficient to cause severe recurrent hypoglycemia does not result in an increase in either SMC/IGF-I or IGF-II concentrations in plasma.

Child, Preschool↗