Biomedical subjects

S L Blethen

Publications and source records attributed to S L Blethen.

At least 55 records · Page 3Linked to original sources

PubMed1990

Blunted growth hormone responses to clonidine in adolescent girls with early anorexia nervosa. Evidence for an early hypothalamic defect.

We studied growth hormone (GH) levels in 14 adolescents with anorexia nervosa (AN), 12-20 years of age. All had amenorrhea and the duration of symptoms ranged from 2-24 months. There was no difference in unstimulated GH between the girls with AN and endocrinologically normal girls. However, the GH response to the alpha-adrenergic agent clonidine was blunted (less than 10 ng/ml) in 11 of 14 girls with AN. Our results of a normal basal GH level and blunted response to stimulation is in contrast to some reports of high basal GH levels and an exaggerated response to pituitary stimulation although it agrees with other studies. Our patient population was younger and at an earlier stage of the disease (12 with symptoms for less than 1 year) than the AN patients previously reported to have elevated GH secretion. In view of studies that report an elevated GH response to growth hormone releasing factor, our results suggest that the AN patient's abnormalities in GH secretion may result from an abnormal hypothalamic response to adrenergic stimuli. This hypothalamic abnormality might also contribute to the growth failure seen in adolescent girls with AN.

Adolescent↗

PubMed1990

Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children.

Demographic, diagnostic, and baseline clinical data were collected for a large cohort (N = 2331) of children who started treatment with biosynthetic human growth hormone (GH) between October 1985 and October 1987. Eighty-one percent met classic criteria for GH deficiency and were classified as having idiopathic GH deficiency (59%), organic GH deficiency (18%), or septo-optic dysplasia (4%). The remaining 19.8% had short stature of varied causes. Height standard deviation score at diagnosis, maximum GH response to stimulation, and heights of parents were examined according to gender, race, age at diagnosis, and previous treatment history. The predominance of boys in all subgroups except septooptic dysplasia, and the observation that girls with idiopathic GH deficiency were comparatively shorter than boys at diagnosis, suggest ascertainment bias. Black children with idiopathic GH deficiency were shorter than white children at diagnosis, and their low overall representation (6.0%) compared with their percentage in the at-risk population (12.9%) also suggest ascertainment bias among races. These data provide a profile of GH deficiency as it is currently defined and expose possible inherent biases in the diagnostic process. Now that GH supply is no longer limited, criteria for its use should be formulated to avoid apparent underascertainment or late diagnosis of GH deficiency in girls and black children.

Adolescent↗

PubMed1990

Characterization of digoxin-like materials in human cord serum.

Human cord serum contains substantial amounts of materials that cross-react in radioimmunoassays for digoxin. The average content of digoxin-like immunoreactivity in mixed cord serum is 0.3 +/- 0.05 ngE/ml compared to less than 0.05 ngE/ml in serum from normal adults. After solvent extraction, the major digoxin-like materials present in cord serum coelute on Sephadex LH-20 column with the steroid sulfate fraction. The steroid sulfates are digoxin-like materials because they cross-react in the digoxin RIA. If the amount of dehydroepiandrosterone sulfate, 16 alpha-hydroxydehydroepiandrosterone sulfate, and 15 beta-hydroxydehydroepiandrosterone sulfate present in cord serum and the amount of digoxin-like material present in the same serum are considered, then up to 90% of the digoxin-like materials present can be accounted for on the basis of the steroid sulfates present. However, although steroid sulfates contribute to the digoxin immunoreactivity in both serum and breast cyst fluid, digoxin-like materials are present in breast cyst fluid that are not present in cord serum.

Cross Reactions↗

PubMed1989

Serum levels of dehydroepiandrosterone sulfate as determined by commercial kits and reagents.

We measured serum dehydroepiandrosterone sulfate (DHEA-S) levels by nine different radioimmunoassay (RIA) methods. Although each method was adequate for determining the amount of authentic DHEA-S, there were marked differences observed between the methods when serum samples were tested. Further, the pattern of these differences varied in different clinical situations. We suggest that the differences in the apparent DHEA-S content resulted from the presence of structurally related compounds which differ in their cross-reactivity in the different RIAs. One of these cross-reacting materials may be a functional androgen.

Adult↗

PubMed1989

Overnight dexamethasone suppression test: normal responses and the diagnosis of Cushing's syndrome.

Serum cortisol levels were measured the morning after the administration of 1 mg of dexamethasone. Only 5 of 190 subjects had serum cortisol levels greater than 2 micrograms/dL. Thus, the normal value after dexamethasone suppression is less than 2 micrograms/dL rather than less than 5 micrograms/dL as has generally been accepted. The distinction is important because some individuals with Cushing's syndrome partially suppress their cortisol levels to less than 5 but more than 2 micrograms/dL during the test procedure. Thus, the use of 5 micrograms/dL as the normal value may lead to an unnecessary delay in diagnosis.

Adolescent↗

PubMed1989

Dehydroepiandrosterone sulfate levels are not suppressible by glucocorticoids before adrenarche.

We measured dehydroepiandrosterone sulfate (DHEA-S) levels in children before and after high dose prednisone therapy. In older children (postadrenarchal), there was a 70% decrease in DHEA-S levels after 1 week. However, even after a month of therapy, DHEA-S was detectable in serum. In contrast, in younger (preadrenarchal) children, the low initial DHEA-S levels were not decreased by prednisone therapy. These findings suggest that there are two distinct regulatory pathways leading to DHEA-S, one of which is independent of ACTH.

Adolescent↗

PubMed1988

Dehydroepiandrosterone sulfate (DHEA-S) and DHEA-S-like compounds in fibrocystic disease of the breast.

We assayed Type 1 (high K+) and Type 2 (high Na+) human breast cyst fluids for DHEA-S. When an antibody specific for the 3-sulfoconjugate end of DHEA-S was used, Type 1 cyst fluids (n = 18) showed a content of 114 +/- 68 micrograms/mL (mean +/- sigma) and Type 2 cyst fluids (n = 14) of 35 +/- 17 micrograms/mL (P less than 0.01). Using an antibody specific for the D-ring, the results were 151 +/- 91 micrograms/mL and 51 +/- 32 micrograms/mL, respectively (P less than 0.01). The apparent concentrations of DHEA-S were statistically different, even though both assays gave equal results in serum from normal adults. The presence of other compounds in individual cyst fluid samples was examined by extraction and chromatography. DHEA-S immunoreactivity was found in both early and late eluting fractions in Type 1 cyst fluids and in late eluting fractions from Type 2 cyst fluids. Only the late eluting fraction from Type 2 fluids had approximately equal immunoreactivity with both antibodies. In addition to authentic DHEA-S, breast cyst fluids contain other materials that react with DHEA-S antibodies. Radioimmunoassays for DHEA-S in cyst fluid must be specifically validated because of the presence of these compounds.

Body Fluids↗

PubMed1987

Steroid metabolic disturbances in Prader-Willi syndrome.

We have studied steroid sulfate conjugates in serum samples from 17 children with Prader-Willi syndrome (PWS) by extraction, enzymatic hydrolysis and chromatography of the hydrolysed, free steroids. The chromatograms in patients with PWS can be divided into 2 classes. Ten (4 with the deletion on chromosome 15 and 6 without) of 17 had a normal pattern with dehydroepiandrosterone (DHEA) as the only steroid detected. However, 7 out of 17 (3 with the deletion and 4 without) had a very different pattern. The chromatogram derived from these hydrolysates had 5 major peaks. One of these was DHEA; a second peak was tentatively identified as 16 alpha-hydroxy-DHEA on the basis of column retention time and immunoreactivity. The remaining 3, more polar, compounds have not yet been identified. The presence of unusual steroid sulfoconjugates in serum may correlate with other features of PWS and may be the basis for dividing PWS into two separate disease states: a) PWS-1 associated with DHEA-S as the only sulfo-conjugate and b) PWS-2 associated with unusual sulfo-conjugates. One interesting possibility is that these sulfo-conjugates may have a hormonal function, even though no function has yet been recognized for DHEA-S. Then, PWS may be the common clinical manifestation of a variety of different defects in the sulfo-conjugate metabolic pathway.

Adolescent↗

PubMed1987

Growth in children with a craniopharyngioma.

Although most children with craniopharyngiomas have multiple hormone deficiencies, some will have normal growth with hyperphagia and obesity postoperatively. Many later fail to maintain this growth. If growth hormone (GH) treatment is not instituted at this time, adult height will be compromised. Normal or accelerated growth following surgery does not indicate the presence of normal GH secretion nor insure continued growth. Children with this syndrome should have careful follow-up with accurate growth measurements so that GH replacement therapy can begin when indicated.

Adrenocorticotropic Hormone↗

PubMed1986

Clinical studies with recombinant-DNA-derived methionyl human growth hormone in growth hormone deficient children.

Thirty-six children with growth hormone deficiency were treated for up to 48 months with methionyl human growth hormone (hGH) synthesised by DNA recombinant methods. The growth rate for these children increased from 3.2 +/- 1.1 cm/yr to 10.5 +/- 2.2 cm/yr (mean +/- SD). This was similar to the effect of pituitary hGH in ten GH deficient children, 3.8 +/- 1.0 to 10.1 +/- 1.1 cm/yr. Serum somatomedin C rose from 0.26 +/- 0.23 U/ml to 0.79 +/- 0.53 U/ml after 6 months of methionyl-hGH therapy, similar to the effect of pituitary hGH. The incidence of antibody formation to methionyl-hGH was higher than that observed with pituitary hGH (Kabi) but poor growth was observed only in the one patient on methionyl-hGH who acquired high-titre high-binding-capacity antibodies to hGH. No consistent changes in levels of antibodies to Escherichia coli proteins were detected. No other allergic manifestations or systemic side-effects were demonstrable.

Adolescent↗

PubMed1986

18q deletion syndrome in a child with steroid-17,20-lyase deficiency.

The del (18q) syndrome is characterised by poor growth, variable mental retardation, facial dysmorphism, and abnormalities of the genitalia. In genetic males, genital abnormalities vary from testicular ectopia, and microphallus to severe hypospadias. Genetic females frequently have hypoplasia of the labia minora. We describe a child with del (18q) syndrome and severe ambiguous genitalia. Serum testosterone after 4 doses of hCG (5000 IU/m2/dose) was only 50 ng/dL (expected greater than 300 ng/dL). When testicular tissue was incubated with [1,2-3H]progesterone and 17-hydroxy-[4-14C]progesterone, there was synthesis of 17-hydroxy-[1,2-3H]progesterone but no further metabolism of 17-hydroxyprogesterone to androgens. These data suggested the presence of steroid-17,20-lyase deficiency. In order to determine if steroid-17,20-lyase deficiency was a common feature in del (18q) syndrome we examined 6 other patients (3 girls; 3 boys) with a deletion of the long arm of chromosome 18 distal to band q21. All 6 had dehydroepiandrosterone sulfate (DHEA-S) levels which were lower than those of age-matched controls. Four had delayed puberty. Serum testosterone levels were also low in 2 of the 3 affected boys. These results together with the findings in the index case suggest that a structural or regulatory gene for steroid-17,20-lyase may be located on the long arm of chromosome 18, distal to band q21.

Abnormalities, Multiple↗

PubMed1986

Outcome in children with normal growth following removal of a craniopharyngioma.

Ten children who had normal or excessive growth rates following surgical removal of a craniopharyngioma have been followed. Final adult heights for three were more than 2.5 standard deviations below the mean adult height for sex. Nine of the 10 children showed a deceleration in growth rate that occurred 1.5-6 years following surgery. The deceleration in linear growth did not appear to correlate with changes in weight gain, somatomedin-C, or the integrated insulin response to an oral glucose load. These results suggest that the mechanisms whereby some children with growth hormone deficiency have normal growth rates following neurosurgic procedures are complex. The authors recommend that these children have continued follow-up so that growth hormone therapy may be instituted when appropriate.

Body Height↗

PubMed1986

Adrenal steroid secretion in girls with pseudoprecocious puberty due to autonomous ovarian cysts.

To evaluate the role of adrenal steroids in pseudoprecocious puberty due to large ovarian follicular cysts, we studied the serum 17-hydroxyprogesterone response to a combination of dexamethasone suppression followed by iv ACTH administration in two girls and compared the results to those in girls with premature thelarche, normal prepubertal girls, and a girl with true precocious puberty. Although basal serum 17-hydroxyprogesterone levels were normal in all subjects, there was incomplete suppression of 17-hydroxyprogesterone with dexamethasone in the two girls with pseudoprecocious puberty and large ovarian cysts. The 17-hydroxyprogesterone response to ACTH was much greater in these girls (360 and 540 ng/dl) than in the girls with other types of precocious puberty (mean +/- SD, 71 +/- 15 ng/dl) or in normal prepubertal girls (80 +/- 20 ng/dl). The girls with large ovarian cysts had decreased gonadotropin responses to GnRH, which were reversed subsequent to removal of the cyst. Removal of the ovarian cysts also restored the dexamethasone suppressibility of serum 17-hydroxyprogesterone and abolished the progression of pubertal development. However, 17-hydroxyprogesterone responses to ACTH were still elevated (160 and 350 ng/dl). Preoperatively, both girls had increased levels of dehydroepiandrosterone sulfate, 16-hydroxydehydroepiandrosterone sulfate, and another unidentified steroid sulfate. These steroid sulfates were also found in the cyst fluid from the one patient from whom the fluid was obtained. These results suggest that steroid production by the adrenal gland may stimulate the development of small ovarian cysts (which may be present in normal prepubertal girls) into large ovarian cysts capable of causing gonadotropin-independent precocious puberty.

17-alpha-Hydroxyprogesterone↗

PubMed1986

Somatomedin production and response to mitogen by lymphocytes in children with growth hormone deficiency.

Studies on the lymphocyte proliferative activity of the sera from growth hormone (GH) deficient patients have resulted in contradictory observations. The ability of lymphocytes to synthesize somatomedin-C (Sm-C) and thus account for a normal proliferative activity (previously observed by us) of the GH-deficient sera was studied, by measuring Sm-C concentration in the culture medium using a standard radioimmunoassay for Sm-C. The response of lymphocytes to the mitogen phytohemagglutinin (PHA), as determined by the incorporation of 3H thymidine into DNA, was also studied. The Sm-C concentrations in the cultures reflected the Sm-C concentrations of the respective serum added and did not alter with significant increases in the cell number induced by PHA. The lymphocytes from GH-deficient children and normal children were indistinguishable in their ability to respond to PHA. We conclude that lymphocyte proliferation in short-term culture, was not associated with an increase in Sm-C and that in the lymphocyte proliferation assay the sera and the lymphocytes from GH-deficient children respond similarly to the sera and lymphocytes from normal children.

Adolescent↗

PubMed1985

Hypopituitarism and septooptic "dysplasia" in first cousins.

Although familial forms of hypopituitarism are known, to our knowledge familial septooptic "dysplasia" in association with hypopituitarism has not been reported. We describe two first cousins with panhypopituitarism, one of whom had septooptic dysplasia. We discuss the possibility that septooptic dysplasia-hypopituitarism may be inherited as an autosomal dominant, or recessive, or multifactorial trait.

Adult↗

PubMed1985

Dehydroepiandrosterone (DHEA) measurements in cord blood.

Antibodies to dehydroepiandrosterone (DHEA) can be generated by coupling DHEA to carrier proteins. This report describes the use of antibodies to three different DHEA-protein complexes for the measurement of DHEA in serum and cord plasma. Each of the three antibodies produces an assay with equivalent results in serum from adults and older children. However, with cord plasma samples, two of the antibodies detected much more cross-reacting material than was detected with the third antibody. In order to determine the basis for this discrepancy, a pool of cord plasma was extracted in a manner similar to that used in the assay procedure. The steroids in the extract were separated by chromatography on a Sephadex LH-20 column and individual fractions were assayed for DHEA with each of the antibodies. There were several peaks of cross-reacting material present in cord blood that were not present in comparable amounts in serum from adults. These results indicate that assays for DHEA need to be separately validated with samples from adults and from infants.

Adult↗

PubMed1985

Partial deficiency in 17-ketosteroid reductase presenting as gynecomastia.

We report a 14 year-old male with severe, long-lasting gynecomastia. Baseline serum androstenedione levels were elevated compared to testosterone levels (330 ng/dl vs 28 ng/dl). In order to evaluate testosterone biosynthesis by this patient in more detail, androstenedione, testosterone, dehydroepiandrosterone (DHEA) and estradiol responses to a single dose of hCG were measured. The responses observed were different from those reported in normal males in two respects: 1) there was no immediate rise in testosterone two to four hours after the injection of hCG, and 2) levels of androstenedione and estradiol at 24, 36 and 48 hours after injection were much higher than expected. We postulate that a partial defect in testicular 17-ketosteroid reductase activity was responsible for the abnormal androstenedione to testosterone ratio in our patient. This, in turn, lead to an increased peripheral synthesis of estrogens and marked gynecomastia.

17-Hydroxysteroid Dehydrogenases↗

PubMed1985

Reversal of Bartter's syndrome by renal transplantation in a child with focal, segmental glomerular sclerosis.

A four-year-old girl with growth failure and clinical and laboratory evidence of Bartter's syndrome responded to indomethacin treatment with decreased urinary prostaglandin excretion, symptomatic and chemical improvement, and accelerated growth. Large doses of aspirin produced a comparable decrease in prostaglandin excretion but no improvement in any other metabolic abnormality thus suggesting that abnormalities in prostaglandins were the result rather than the cause of the electrolyte abnormalities. Progressive renal insufficiency while on indomethacin prompted a renal biopsy, which revealed morphological changes of focal, segmental glomerular sclerosis. Subsequently, the child underwent renal transplantation with complete resolution of symptoms and abnormal metabolic findings. This observation suggests that extrarenal factors were not responsible for the development of Bartter's syndrome in this child.

Alkalosis↗