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Biomedical subjects

D M Styne

Publications and source records attributed to D M Styne.

At least 37 records · Page 2Linked to original sources
PubMed1991

Drug treatment in precocious puberty.

Precocious puberty, as defined by the onset of pubertal development before the age of 8 years in girls or 9 years in boys, can be classified into central and peripheral aetiologies. Central precocious puberty (CPP) results from early activation of the hypothalamic-pituitary-gonadal axis and has similar physical and hormonal characteristics to normal puberty. Extrapituitary gonadotrophin secretion or independent sex steroid secretion results in peripheral precocious puberty (PPP). Precocious puberty is characterised by rapid growth and advancement of skeletal age. The skeletal advancement is greater than the growth increase, so that final adult height is compromised. Long-acting gonadotrophin releasing hormone (GnRH) agonists are the current therapy of choice for central precocious puberty, having demonstrated effectiveness in halting the precocious development associated with this condition with minimal side effects. GnRH agonists are not effective as therapy for peripheral precocious puberty, but a number of other agents have been used with some success. These include androgen antagonists, testolactone, ketoconazole, and medroxyprogesterone acetate. The use of GnRH agonists has been associated with an increase in predictions of final height; however, continuing studies in treated cohorts are necessary to determine the true benefit of any of these agents on increasing ultimate height.

Adolescent↗
PubMed1991

Serum insulin-like growth factor 1 concentrations in the developing rhesus monkey.

We studied the developmental pattern of serum IGF-1 concentrations in the rhesus monkey in cross-sectional and longitudinal manners. Values were lower in infants with a significant rise at the onset of puberty. Females values were lower than males except for pregnant females. There was a correlation of IGF-1 values with body weight in the males. Longitudinal study of six animals proved this age dependence of IGF-1 values. The rhesus monkey has a pattern of serum IGF-1 concentrations similar to that of the human being.

Age Factors↗
PubMed1991

The growth hormone secretory response to growth hormone releasing factor in the developing rhesus monkey.

We studied the development of the GH response to growth hormone releasing hormone (GHRH) using two doses of GHRH. The newborns demonstrated higher baseline GH and responses to GHRH than animals of any older age. There was no difference noted between the rise in GH in male and female subjects with 10 mcg/kg vs 1 mcg/kg. Serum cortisol concentrations did not correlate with serum GH concentrations. These developmental patterns of serum GH are similar to those known in the human being.

Analysis of Variance↗
PubMed1991

The treatment of precocious puberty.

Long-acting GnRH agonists are the treatment of choice for central precocious puberty. GnRH agonists are not effective in peripheral precocious puberty, but a number of other agents, including medroxyprogesterone acetate, ketoconazole, testolactone, and androgen antagonists, may be useful.

Androgen Antagonists↗
PubMed1991

Puberty and its disorders in boys.

The secular trend toward an earlier age of puberty implicates health and nutrition as major determinants of the onset of sexual maturation. The pattern of hypothalamic stimulation of pituitary gonadotropin secretion causing gonadal steroid secretion that is active in the fetus, subdued in the child, and again awakened in the peripubertal period is well described, although the specific trigger of the initiation of puberty is unknown. Pubertal delay may have a cause in the CNS or in the gonad. Constitutional delay in pubertal development, a variant of normal, is difficult to differentiate from isolated gonadotropin deficiency, a permanent condition. However, a myriad of congenital defects, tumors, injuries, and infections can lead to hypogonadotropic hypogonadism, which may be diagnosed by associated physical findings. Gonadal abnormalities are characterized by elevated gonadotropin concentrations and often are associated with specific physical features. Early pubertal development may also be divided into etiologies based in the CNS or in other parts of the body. Idiopathic precocious puberty, in which the endocrine profile is identical to that of normal puberty, is seen in the early childhood period or as a minor variation from the normal range of the onset of pubertal development. Tumors of the CNS, however, are more often responsible for the youngest childhood cases of complete precocious puberty. Incomplete precocious puberty in boys can be caused by androgen production from the gonads or adrenal glands or can be caused by autonomous production of hCG. Variations of pubertal development are self-limited, although they may awaken parental or patient concerns. Thus, premature adrenarche is best differentiated from more serious and treatable causes of androgen production. Gynecomastia is usually treated with reassurance.

Adolescent↗
PubMed1990

Diagnosis and management of precocious puberty.

The onset of pubertal development before the age of 8 years in girls or 9 years in boys constitutes precocious puberty. There are numerous causes of precocious puberty, which can be classified as central or peripheral precocious puberty. Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis and thus presents with physical and hormonal findings similar to those found in normal puberty. Peripheral precocious puberty results from extrapituitary gonadotropin secretion or secretion of sex steroids independent of pituitary gonadotropins. All types of precocious puberty are characterized by rapid growth and advancement of skeletal age, leading to the paradox of the tall child becoming a short adult as a result of premature epiphyseal fusion. Long-acting GnRH agonists afford effective, selective, and reversible therapy of central precocious puberty without significant toxicity. GnRH agonists are not effective in managing the premature sexual maturation associated with peripheral precocious puberty, but a number of other agents have been used with some success. These agents include testolactone, ketoconazole, and medroxyprogesterone acetate. GnRH agonist treatment leads to an increase in predicted final height. To determine the true benefit of any of these agents in increasing ultimate height, there is a need for continuing studies in treated cohorts to follow growth patterns until adult stature is achieved.

Child↗
PubMed1990

Longitudinal changes in growth hormone response to growth hormone-releasing hormone in neonatal rhesus monkeys.

To determine whether differential response to growth hormone-releasing hormone (GHRH) could cause the developmental changes seen in growth hormone (GH) secretion, we administered 10 micrograms/kg GHRH (1-44 NH2) to a group of four unanesthetized, fasted, rhesus monkeys via acutely placed venous catheters at 1, 7, 14, and 28 d postnatal age. Serum GH was assayed by hGH RIA in sera collected at -60, -30, 0, 15, 30, 45, 60, and 90 min relative to the GHRH bolus. Serum cortisol was measured by ELISA in the 0-, 30-, and 60-min samples. Differences between age groups were analyzed by repeated measures analysis of variance and paired t tests. Mean basal GH levels were higher at 1 d (9.4 +/- 1.2 micrograms/L, mean +/- SEM) than at 7 (5.5 +/- 0.4), 14 (5.6 +/- 0.5), and 28 d (5.3 +/- 0.5) of age. There were no other significant differences in mean basal GH values between the age groups. Mean post-GHRH GH concentrations decreased significantly with each age after 1 d (22.6 +/- 1.6): 7 d (16.4 +/- 1.3); 14 d (11.3 +/- 1.0); and 28 d (7.9 +/- 0.9). Similarly, mean delta-GH values decreased with each increase in age from 1 d (15.0 +/- 1.9): 7 d (10.9 +/- 1.6); 14 d (5.9 +/- 1.1); and 28 d (2.7 +/- 0.8). Serum cortisol was not correlated with serum GH at any age. Our study demonstrates decreasing basal GH concentration and GH responses to GHRH with advancing age from 1 to 28 d in the rhesus monkey.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1990

Changes in basal and stimulated growth hormone secretion in the aging rhesus monkey: a comparison of chair restraint and tether and vest sampling.

We studied basal serum GH and GH responses to iv clonidine and insulin-induced hypoglycemia in a group of four young (5-7 yr old) and four older (10-14 yr old) adult male rhesus monkeys under two restraint conditions, chair adaptation and a tether and vest system, to determine what changes in GH secretion occur with aging. The serum GH response to iv administration of GH-releasing hormone (GHRH) was also studied in the groups under tether and vest restraint. Serum samples were collected every 15 min and assayed for GH using a human GH RIA and for cortisol using an enzyme-linked immunosorbant assay. GH and cortisol concentrations in the young and older groups were analyzed with analysis of variance (ANOVA). In the chaired studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (2.7 +/- 0.8 vs. 3.5 +/- 0.5 micrograms/L; P = 0.0002). Prestimulation GH was lower before clonidine and insulin in the older chaired group (1.1 +/- 0.5 and 2.3 +/- 0.6 micrograms/L, respectively) compared to the younger group (3.6 +/- 0.8 and 3.8 +/- 0.7 micrograms/L, respectively; P less than 0.001). Poststimulation GH was lower after clonidine and insulin in the older chaired group (3.2 +/- 2.4 and 7.1 +/- 2.8 micrograms/L, respectively) compared to the younger chaired group (6.3 +/- 2.2 and 10.3 +/- 3.0 micrograms/L, respectively; P less than 0.05), but the differences in GH increments were not statistically significant. In the tether and vest studies the older animals had a lower mean 6-h basal GH concentration than did the younger animals (1.7 +/- 0.4 vs. 3.5 +/- 1.2 micrograms/L; P less than 0.0001). Prestimulation GH concentrations were also lower in the older tethered animals before clonidine (2.1 +/- 0.3 micrograms/L) and GHRH (1.4 +/- 0.2 micrograms/L) compared to levels in the younger animals (3.1 +/- 0.9 and 3.2 +/- 0.7 micrograms/L; P = 0.0023 and P = 0.0001, respectively). The younger tethered animals had greater poststimulation responses to clonidine (8.7 +/- 3.0 micrograms/L), insulin (8.8 +/- 3.6 micrograms/L), and GHRH (6.0 +/- 2.4 micrograms/L) than the older animals (3.8 +/- 0.9, 3.9 +/- 2.5, and 2.9 +/- 0.7 micrograms/L; P less than 0.0001, P = 0.0025, and P less than 0.03, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1989

Hormone ontogeny in the ovine fetus and neonatal lamb. XX. Effect of age, breeding season, and twinning on the growth hormone (GH) response to GH-releasing factor: evidence for a homeostatic role of fetal GH.

The ovine GH (oGH) response to GRF (1-44 amide) was evaluated in 74 chronically catheterized fetal and neonatal lambs. After a 1-h control period, GRF was administered iv, and the oGH response was studied during the next 60 min. The following variables were analyzed: GRF dose, fetal or neonatal age, breeding season, and singleton or multiple pregnancy. One and 10 micrograms/kg GRF elicited a similar oGH response, which was greater (P less than 0.001) than the response to 0.1 microgram/kg GRF. GRF-stimulated oGH release was strikingly age dependent. The mean peak incremental oGH response in fetuses of 89-122 days gestation (294 +/- 55 ng/ml) was higher (P less than 0.05) than that in fetuses of 127-145 days gestation (136 +/- 19 ng/ml); the fetal response was much greater (P less than 0.005) than the mean peak increment in neonatal lambs (46 +/- 7 ng/ml). A remarkable difference in basal and GRF-induced oGH secretion was observed in both fetuses and lambs of ewes bred in the normal breeding season (on-season) and those bred out of season (off-season). In the neonatal lamb, the mean basal oGH concentration was higher (P less than 0.005) in the on-season (12 +/- 2 ng/ml) than in the off-season (7 +/- 0.5 ng/ml) neonatal lambs, as was the mean peak incremental oGH response to GRF (70 +/- 12 vs. 33 +/- 7 ng/ml; P less than 0.01). In contrast, in singleton, late gestational fetuses (127-145 days), the mean basal oGH concentration was lower (P less than 0.03) in the on-season (74 +/- 9 ng/ml) than in the off-season (124 +/- 18 ng/ml) fetuses, as was the mean peak incremental oGH response to GRF (136 +/- 9 vs. 292 +/- 41 ng/ml; P less than 0.005). Further, compared to the on-season, late gestational singletons, on-season twin fetuses had higher (P less than 0.0001) basal oGH levels (199 +/- 19 ng/ml) and peak incremental oGH responses (248 +/- 11 ng/ml). Moreover, off-season twin fetuses had the highest basal GH concentrations and the most striking increment in GH concentration after GRF treatment of any of the groups. The strikingly age-dependent pattern of the GRF-induced oGH response in fetal and neonatal lambs is compatible with the concept that the inhibitory influences or their effects on the somatotrope increase gradually during late gestation and sharply at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1988

The nonhuman primate as a model of growth hormone physiology in the human being.

Our review confirms the close correlation of the physiology of GH secretion in the nonhuman primate and the human subject which has not been seen in any other animal model, at least from the studies available to date. Except for a discrepancy in the relationship of GH secretion during early sleep, there are no significant differences between the species that can not likely be explained by methodological differences. Even the discrepancy between nighttime GH secretion may be due to methods of studying the nonhuman subjects. But methodological problems are at the heart of the problem in primate research. Primates are expensive to buy ($800-$1200 is not unusual for an adult male), expensive to house ($2-$3 per day is customary), dangerous to work with (bodily injury and serious infections are equally worrisome to handlers), exquisitely sensitive to environmental factors (as noted above), and above all, the subject of appropriate concern from animal use committees: these factors easily explain the relative dearth of primate studies on GH physiology compared to rodent studies. Problems of handling the animals and ensuring their stable state are helped to large degree by facilities such as the Regional Primate Facilities in the United States. The studies reviewed above should clearly demonstrate that the primate model, in spite of all the difficulties involved, is invaluable in investigating physiological phenomenon impossible to pursue in the human being. But only studies offering fastidious attention to detail in this potentially unstable model of GH physiology are likely to answer more questions than they raise.

Amino Acids↗
PubMed1986

Transient neonatal 'athyreosis' resulting from thyrotropin-binding inhibitory immunoglobulins.

Recognition of transient forms of neonatal hypothyroidism is difficult because of the urgency of thyroxine treatment. In the present report the first child born to a mother with Graves' disease developed transient hyperthyroidism during the newborn period. The mother underwent radioactive iodine treatment and was maintained euthyroid on l-thyroxine. Two subsequent children were detected by newborn thyroid screen to have low thyroxine and markedly elevated serum thyrotropin (TSH) levels. Technetium 99 metastable and iodine 123 scans at 22 days of age showed the second child to be athyreotic. The third child was not scanned. All three children were nongoitrous at birth. Patients 2 and 3 had continuous TSH suppression with thyroxine therapy for 3 and 4 years. Thyroid function measurements after discontinuation of therapy for 8 weeks were normal, and both children had normal 123I thyroid scans. The mother was found to have potent TSH-binding inhibitory immunoglobulin (TBII) levels in her serum (85.5%). A fourth child with low thyroxine and elevated TSH was born to a mother on a regimen of l-thyroxine for hypothyroidism. 99mTc scan at 26 days of age showed no thyroid tissue and was normal at 3 months. TBII activity was 35% in the maternal serum and absent in the infant's serum. The above laboratory and clinical data are compatible with the blocking nature of TBII, resulting in transient newborn hypothyroidism and an athyreotic appearance on scan. The TBII measurement can be a useful predictor of neonatal hypothyroidism as well as confirm the transient nature of the disease in newborns.

Adult↗
PubMed1985

Familial functional anorchism: a review of etiology and management.

Identical male twins with small penes and bilateral unpalpable gonads were unresponsive to human chorionic gonadotropin stimulation. Both infants had elevated levels of gonadotropins. The size of the penis did not meet fully the criteria for micropenis and the organ was responsive to testosterone therapy. The use of primary human chorionic gonadotropin stimulation followed by testosterone measurements is indicated for children with cryptorchidism in whom the etiology of micropenis is in doubt. We report the first observation of anorchism in identical twins.

Chorionic Gonadotropin↗
PubMed1985

Hormone ontogeny in the ovine fetus. XVIII. The effect of an opioid antagonist on luteinizing hormone secretion.

Endogenous opioid-like peptides influence gonadotropin release in adult animals and man; however, the role of these peptides in the regulation of fetal LH secretion is not known. We administered naloxone hydrochloride (1.3 mg/kg iv), a specific opioid receptor antagonist, to 22 chronically catheterized ovine fetuses of gestational ages 94-143 days (term = 147 days). As a control, each fetus also received the vehicle on a separate occasion, the sequence of the studies being randomized. After the administration of naloxone, LH secretion increased from 38.6 +/- 5.8 to 114 +/- 21 ng/h ml-1 (P less than 0.001); LH release was not affected by administration of the vehicle. Morphine (13 mg/kg) and naloxone (1.3 mg/kg) were administered together to three fetuses (gestational age 94-105 days); LH secretion was sharply reduced from 411 +/- 14.3 ng/h ml-1 after naloxone alone to 53 +/- 17.5 ng/h ml-1 after the administration of both naloxone and morphine (P less than 0.01). The response to naloxone varied with gestational age. Fetuses of 94-115 days showed a significantly higher increment in LH secretion when given naloxone (112.3 +/- 30.7 ng/h ml-1) than did older fetuses of gestational age 126-143 days (64.8 +/- 20.8 ng/h ml-1) (P less than 0.02). These findings indicate that, in the ovine fetus endogenous opioid-like peptides exert a tonic suppressive effect on LH secretion at least as early as 94 days gestation. Moreover, the effectiveness of naloxone in augmenting LH release decreases with advancing gestational age. This latter observation supports the concept that, in the ovine fetus, endogenous opioid tone is not the sole factor involved in the dampened fetal LH secretion which is characteristic of late gestation.

Animals↗
PubMed1985

Treatment of true precocious puberty with a potent luteinizing hormone-releasing factor agonist: effect on growth, sexual maturation, pelvic sonography, and the hypothalamic-pituitary-gonadal axis.

We used the LHRH agonist D-Trp6-Pro6-N-ethylamide LHRH (LHRH-A) to treat 19 children (12 girls and 7 boys) with true precocious puberty. Fourteen patients had idiopathic true precocious puberty, 4 had a hamartoma of the tuber cinereum, and 1 had a hypothalamic astrocytoma. Basal gonadotropin secretion and responses to native LHRH decreased within 1 week of initiation LHRH-A therapy, and sex steroid secretion decreased within 2 weeks to or within the prepubertal range. Ultrasonographic evaluation of the uterus indicated a postmenarchal size and shape in all 11 girls studied before treatment, which reverted to prepubertal size and configuration in 5 girls during LHRH-A therapy. The enlarged ovaries decreased in size and the multiple ovarian follicular cysts regressed. Sexual characteristics ceased advancing or reverted toward the prepubertal state in all patients receiving therapy for 6-36 months. All 5 girls with menarche before therapy had no further menses. Three girls had hot flashes after LHRH-A-induced reduction of the plasma estradiol concentration. Height velocity, SDs above the mean height velocity for age, and SDs above the mean height for age decreased during LHRH-A therapy; the velocity of skeletal maturation decreased after 12 months of LHRH-A therapy and was sustained during continued therapy over 18-36 months. In 4 patients, a subnormal growth rate (less than 4.5 cm/yr) occurred during LHRH-A therapy. Six patients had cutaneous reactions of LHRH-A, but no demonstrable circulating antibodies to LHRH-A. In 2 patients in whom LHRH-A therapy was discontinued because of skin reactions, precocious sexual maturation resumed at the previous rate for the ensuing 6-12 months; subsequently, they were desensitized to LHRH-A, and during a second course of therapy, their secondary sexual development and sex steroid levels again quickly decreased. LHRH-A proved an effective and safe treatment for true precocious puberty in boys as well as girls with central precocious puberty whether of the idiopathic type or secondary to a hamartoma of the tuber cinereum or a hypothalamic neoplasm.

Age Determination by Skeleton↗
PubMed1985

Somatomedin-C in normal puberty and in true precocious puberty before and after treatment with a potent luteinizing hormone-releasing hormone agonist.

To explore further the relationship of gonadal sex steroids to the rise in somatomedin-C (Sm-C) during puberty, we studied a group of children with true precocious puberty before and after treatment which suppressed sex steroid output. Plasma estradiol and testosterone and serum acid-ethanol-extractable Sm-C were determined by specific RIAs in 7 boys and 12 girls with true precocious puberty before and at regular intervals during treatment with a potent LHRH-agonist (LHRH-A), D-Trp6-Pro9-NEt-LHRH. For comparison, Sm-C and sex steroid concentrations were determined in 266 normal adolescents and 37 normal prepubertal children, 1-9 yr of age. The mean +/- SEM Sm-C levels in normal male individuals peaked at 15 yr (2.46 +/- 0.23 U/ml) and at pubertal (genital) stage III (2.29 +/- 0.19 U/ml), and those in normal females reached their highest concentration at 12-15 yr of age and at pubertal (breast) stage III (2.47 +/- 0.15 U/ml). Sm-C concentrations correlated better with pubertal (genital or breast) stage than with chronological age for both sexes and better with testosterone levels in males than with estradiol levels in females. The mean +/- SEM Sm-C concentrations in both males and females with true precocious puberty were 2.07 +/- 0.16 U/ml before therapy and decreased significantly to 1.52 +/- 0.13 U/ml after 6 months of therapy. The mean Sm-C level of the patients remained significantly elevated for chronological age, but decreased into the normal range for bone age after 6-12 months of therapy. Sm-C correlated significantly with testosterone and estradiol levels, but not with growth rate. Mean nighttime GH secretion decreased significantly after 6 months of LHRH-A therapy. In summary, children with true precocious puberty have Sm-C elevations typical of normal puberty. The decrease in Sm-C levels after suppression of gonadal sex steroid output with LHRH-A is evidence that sex steroids are necessary to induce this elevation in Sm-C concentration. The decrease in GH secretion during LHRH-A therapy suggests that the effect of sex steroids on Sm-C levels during normal puberty is mediated, at least in part, through stimulation of GH secretion.

Adolescent↗
PubMed1984

Treatment of Cushing's disease in childhood and adolescence by transsphenoidal microadenomectomy.

Fifteen unselected children and adolescents with Cushing's disease were treated by transsphenoidal exploration and microadenomectomy. In only three patients was radiographic examination of the sella turcica, including computed tomography, useful in indicating the presence and location of a pituitary microadenoma. Transsphenoidal microadenomectomy corrected hypercortisolism in 14 of the 15 patients; no adenoma was detected in one patient, and one required a second operation six months after the first because of incomplete removal of the adenoma. All 14 lost weight and cushingoid stigmata and had normal or catch-up growth (if epiphyses were not fused) and progression of puberty. In one patient, a recurrence was successfully treated by repeat microadenomectomy six years after the first procedure. The low morbidity and failure rate of the procedure, the low recurrence rate, the rapid amelioration of signs of hypercortisolism, and the preservation of pituitary function in the present study support transsphenoidal microadenomectomy as a low-risk approach to the initial treatment of Cushing's disease in childhood and adolescence.

Adenoma↗
PubMed1984

Hormone ontogeny in the ovine fetus. XVII. Demonstration of pulsatile luteinizing hormone secretion by the fetal pituitary gland.

To determine whether pulsatile gonadotropin secretion occurs in the fetus, plasma immunoreactive ovine LH (oLH) concentrations were determined by homologous RIA in serial samples obtained in 51 chronically catheterized fetuses between 79 and 140 days gestation. Pulsatile secretion of LH was detected in 39 fetuses, with a peak amplitude ranging from 1.2-11.5 ng/ml (mean +/- SD, 4.5 +/- 2.3 ng/ml). The mean plasma oLH concentration between pulses was 0.4 +/- 0.23 ng/ml. The mean amplitudes of the LH pulses were similar in the age range studied, and a sex difference was not detected. The estimated interpulse interval (determined by dividing the total number of hours during which blood samples were obtained by the number of pulses demonstrated) was 2.4 h between 91 and 110 days gestation. The pattern of plasma oFSH concentration was examined in 20 fetuses between 98 and 123 days gestation. Six fetuses with gestational ages between 106 and 115 days had FSH pulses that were equal or more than 2 times the sensitivity of the RIA. This study demonstrates a pulsatile mode of LH secretion by the ovine fetal pituitary as early as 81 days gestation and provides indirect evidence for pulsatile LRF secretion by the fetal hypothalamus and an operative LRF pulse generator by midgestation, the earliest stage in gestation studied.

Animals↗